We play with stem cells!We innovate cancer treatment!

Overview

The ultimate goal of our research is to help people live longer and healthier. Preventing death and repairing the aged/diseased organs are essential to achieve this goal. Cancer is the most common cause of death, and organ failure is the most common feature of aging-related diseases. Therefore, regenerative medicine and cancer precision medicine are key areas of convergence biomedical research to prolong human life in the era of 4th industrial revolution.

Our mission is to make innovative and ground-breaking, convergence stem cell and cancer research and translate our research discoveries for the improvement of health and the cure of diseases. The core values of our research group include highest level of professionalism, creativity, innovation, integrity, motivation, resilience, mutual care and team-work. With this mission and core values in mind, we study these three inter-connected and synergizing research areas of

(1) Stem cell biology & regenerative medicine,

(2) Cancer biology & precision medicine,

(3) Aging & anti-aging medicine.

Lab with K-BioX

Research Summary

Central questions: What are the role of recurrent mutations in stem cell self-renewal, cancer pathogenesis,

and cancer therapeutic resistance?

Stem cells and cancers are tightly inter-related. Stem cells are oftentimes are the cell of origin for cancers. Also cancers have a subpopulation of cells, so called cancer stem cells (CSCs, a.k.a. tumor-initiating cells), which have stem cell-like characteristics and are considered the source of cancer recurrence. On the other hand, cancer is one of major aging diseases, and stem cells and stem-cell derived organs are the potential sources for anti-aging medicine. Therefore, stem cell research and cancer research are cross-connected and mutually applicable.

Our detailed research focuses include, but are not limited to,

I. Identification of tissue stem cells and their self-renewal mechanisms Still many tissue stem cells have not been identified. Furthermore, stem cell self-renewal and expansion are invaluable for regenerative medicine. We have extensive experience and expertise in these areas and will continue to achieve original and more significant research findings to identify and expand stem cells for regenerative medicine.

- We have for the first time identified human and mouse esophageal stem cells (Jeong et al, Gut, 2016), and we are currently trying to identify other tissue stem cells.

II. Organogenesis The ultimate goal of stem cell biology and regenerative medicine is to generate micro-, mini-, and macro-organ to be used for organ transplantation. Although some researchers including our group succeeded in generating epithelial organoids and some of micro-organs derived from ESCs or iPSCs, the destination is still far to reach. We have built up strong experiences and expertise in epithelial stem cell biology and gear up toward organogenesis.

- As the first step toward organogenesis, we have built up our expertise in organoid culture. We have for the first timedeveloped human and mouse esophageal organoids (Jeong et al, Gut, 2016) and other organoids (to be reported). We are also using a lot of other organoids including tracheal and lung organoids (Jeong et al, Cancer Discovery, 2017), and also tumor organoids.

- We are currently trying to develop mini-organs.

III. Development of targeted therapies for cancers Individualized precision medicine will ultimately refine and maximize the cancer treatment effect and minimize the side effects. We have shown that mutations in Keap1-Nrf2 anti-oxidant pathway promote the pathogenesis of lung squamous cell carcinoma by deregulating airway stem cell self-renewal. We further demonstrated that KEAP1/NRF2 mutations confer lung cancers therapeutic resistance and that genetic pre-screening of the mutation status of lung cancers could help us predict cancer recurrence (Jeong et al, Cancer Discovery, 2017). Now we aim to develop novel therapies precisely targeting KEAP1/NRF2 mutant cancers and cancers with other mutations.

IV. Targeting cancer stem cells (CSCs)- You have to remove the root if you want to get rid of weeds. Likewise, CSC theory suggests that we need to eliminate CSCs to cure cancers. CSCs are a subpopulation of cancer cells with the stem cell-like characteristics and are more resistant to chemotherapy and radiation therapy. We are particularly interested in identifying and targeting CSCs in head and neck and lung cancers.

V. Tumor immunology

- Cytotoxic T lymphocytes (CTLs) and Natural Killer (NK) cells are two major players in tumor immunology. We are interested in regulatory pathways of CTLs and NK cells' activation. By modulating those pathways, we aim to develop novel drugs or therapies against cancers.

VI. Stem cell therapy in lung fibrosis- Idiopathic pulmonary fibrosis (IPF) is one of the representative aging diseases. IPF is a progressive, restrictive lung disease. In IPF, lung epithelium becomes thickened and scarred, impairing gas exchange. However, the role of lung stem cells and their niche in IPF pathogenesis has not been well understood. Thus, we aim to further elucidate the role of lung stem cells in IPF pathogenesis and treatment.

Youngtae Jeong (), M.D., Ph.D.

Principal Investigator,Assistant Professor

Department of New Biology atDGIST

Office: E5-311

Tel: +82-53-785-1620

Email: jyt@dgist.ac.kr

Education and Training

1995-2001 M.D., Seoul National University College of Medicine

2001-2002 Intern, Seoul National University Hospital

2005-2009 Ph.D., Johns Hopkins University School of Medicine

Professional Experiences

2009-2010 Postdoc, Whitehead Institute for Biomedical Research (MIT)

2010-2015 Podstoc, Stanford University Cancer Institute

2015-2018 Instructor, Stanford Univ. Department of Radiation Oncology

2018-Current, Assistant Professor, DGIST Department of New Biology

Honors and Awards (Selected)

2020 DGIST Outstanding Research Award

2019 Outstanding Abstract Award, Korean Cancer Association

2016 Abstract Award, Cleveland Cancer Stem Cell Conference

2016 Travel Award, FASEB Science Research Conference

2014 ECFMG Certificate (US Medical License)

2012 Travel Award, Freston Conference

2008 Korean Honor Scholarship, Embassy of Korea, Washington D.C.

2000 Outstanding Field Research Award, LG Global Challenger Program

International Fellowships and Grants

2012-2015 California Institute for Regenerative Medicine

2012 Stanford University School of Medicine

2008-2009 American Heart Association

Byungmoo Oh (), Ph.D.

Postdoctoral Fellow

Education and Training

B.A., Chungbuk National University, Korea

Ph.D., University of Science and Technology, Korea

bmoh@dgist.ac.kr

Baul Lee (), Ph.D.

Postdoctoral Fellow

Education and Training

B.A., Sahmyook University, Korea

Ph.D., SeoulNational University, Korea

Licensed Pharmacist in Korea (2012)

paul36@dgist.ac.kr

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HOME | Stem cell & Cancer

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the world of oncology with the advent of new personalized treatment for a wide array of malignancies. However, a recent study by Mackensen et al has raised the possibility that CAR T cell therapy may also have a role outside of the treatment in cancer, through positive findings that have been published in the treatment of refractory systemic lupus erythematosus (SLE).1

CAR T cell therapy is already an established treatment used in a variety of haematological malignancies. This is relatively recently developed technology, which has rapidly expanded over the last decade with more than 350 studies currently ongoing investigating the use of this treatment in an array of settings (predominantly oncological). For therapeutic use, circulating peripheral T cells are harvested from the patient and isolated from whole blood. These ex-vivo cells are then genetically engineered to express a chimeric antigen receptor against the desired target (in the case of this study the target antigen being CD19, found on B lymphocytes). The basis of the therapy is that these CAR T cells will then target and destroy cells expressing this antigen. The newly engineered T cells are then grown in cell culture before being infused back into the patient. The process takes approximately 2 weeks from T cell isolation to subsequent CAR T cell infusion. Prior to receiving the newly generated T cells, a period of conditioning treatment, which effectively allows for space for CAR T cell expansion within the bone marrow allowing for these new cells to populate, is required. In this study, the investigated used a combination of fudarabine and cyclophosphamide for this. It is also important to consider that the isolation of circulating T cells requires a sufficient quantity of circulating lymphocytes. As a result, the authors decided to taper immunosuppressive therapy before collection of host T cells (in particular this focused on decreasing T cell cytotoxic medication such as cyclophosphamide and mycophenolate three weeks prior to cell collection).

In their recent Nature Medicine publication, the authors demonstrated the use of anti-CD19 CAR T cell therapy in the treatment of 5 patients with severe and refractory SLE. Patients were aged between 18-24 years old and included 4 females and 1 male. Patients had active disease with a SLE Disease Activity Index 2000 (SLEDAI-2K) of 8-16 at the time of treatment. All had cutaneous disease, in addition to proliferative lupus nephritis (Class III or IV) with 2 having overlapping membranous nephritis (Class V). Four of the 5 patients also had joint involvement. All had been treated with glucocorticoids, hydroxychloroquine, mycophenolate and belimumab with 3 receiving cyclophosphamide and 1 treated with rituximab previously. This represents a group of patients with significantly active disease that was refractory to multiple therapies.

Following infusion of CAR T cells, patients were observed in hospital for a total of 10 days prior to discharged (predominantly to monitor for signs of toxicity). In the use of CAR T cells in the treatment of malignancy, an array of side effects can be observed with the therapy. This includes generalized symptoms (such as fevers and headache). More severe effects include cytokine release syndrome and neurotoxicity. Interestingly, in this study in SLE the treatment was very well tolerated without severe consequences noted.

In the subsequent days following infusion of CAR T cells, the authors identified that these cells initially represented only a small subpopulation with the patients circulating T cell repertoire within the first 24 hours, before significantly expanding by day 9 post-infusion (at which point between 11-59% of circulating T cells were CARs). With regards to clinical response, a remarkable improvement was seen within the first 3 months of therapy. Four of the 5 patients achieved a SLEDAI-2K of zero (whilst the remaining patient seeing an improvement from 16 to 2).

Most impressively, there appeared to be a sustained response to this therapy and the authors report not only long-term remission but that this was treatment-free remission! It is quite astonishing that patients with severe disease that was refractory to multiple other agents showed a drastic improvement and ultimately were able to discontinue all therapy including glucocorticoids! The follow-up period is currently only at a maximum of 17 months, however long-term steroid-free response offers hope for a decrease in damage secondary to prolonged exposure to glucocorticoids (including osteoporosis and increased risk of cardiovascular disease).

Aside from being both extremely effective in achieving remission and well tolerated, the authors also importantly showed no significant reduction in vaccine response in the 5 patients treated with CAR T cells therapy, which is of particular interest at present.

In summary, CAR T cell therapy may not be required in many cases of SLE; however, the findings of this study of anti-CD19 directed CAR T cell therapy offers new hope for the most severe and refractory cases. In addition, the sustained long-term effects of treatment plus the ability to withdraw all treatment also confers that the risk of damage and infection (leading causes of morbidity and mortality in SLE) may also be reduced. The future is very exciting!

Reference:

Mackensen A, Mller F, Mougiakakos D, Bltz S, Wilhelm A, Aigner M, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nature medicine. 2022.

More here:
CAR T Cell Therapy Offers a New Hope in the Treatment of Severe and Refractory Systemic Lupus Erythematosus - Rheumatology Network

Cell and gene therapies seek to correct the root cause of an illness at the molecular level. These game-changing medicines are reshaping how we address previously untreatable illnesses transforming peoples lives.

Cell and gene therapy represent overlapping fields of research with similar therapeutic goals developing a treatment that can correct the underlying cause of a disease, often a rare inherited condition that can be life-threatening or debilitating and has limited treatment options.

While these technologies were initially developed in the context of treating rare diseases caused by a single faulty gene, they have since evolved towards tackling more common diseases, says Professor Rafael J. Yez-Muoz, director of the Centre of Gene and Cell Therapy (CGCT) at Royal Holloway University of London.

A powerful example is the chimeric antigen receptor (CAR) T-cell therapies, which have been approved for treating certain blood cancers. The approach involves genetically modifying a patients T cells in the laboratory before reintroducing them into the body to fight their disease.

For the first time, we had an example of gene therapy to treat a more common disease demonstrating that the technology has wide applicability, enthuses Yez-Muoz.

To date, 24 cellular and gene therapy products have received approval from the US Food and Drug Administration (FDA) including life-changing treatments for patients with rare diseases, such as inherited forms of blindness and neuromuscular conditions. A variety of gene and cell-based therapies for both rare and common diseases are also currently in development across many therapeutic areas, offering hope for many more families in coming years.

This webinar will provide an introduction to the regulatory framework for cell and gene therapies and highlight the importance of chemistry, manufacturing and controls. Watch to learn about regulatory concerns, safety and quality testing throughout the product lifecycle and key acronyms and terminology.

Gene therapies seek to introduce specific DNA sequences into a patients body to treat, prevent or potentially cure a disease. This may involve the delivery of a functional gene into cells to replace a gene that is missing or causing a problem or other strategies using nucleic acid sequences (such as antisense oligonucleotides or short interfering RNAs [siRNAs]) to reduce, restore or modify gene expression. More recently, scientists are also developing genome-editing technologies that aim to change the cells DNA at precise locations to treat a specific disease.

The key step in successful gene therapy relies on the safe and efficient delivery of genetic material into the target cells, which is carried out by packaging it into a suitable delivery vehicle (or vector). Many current gene therapies employ modified viruses based on adenoviruses, adeno-associated viruses (AAV), and lentiviruses as vectors due to their intrinsic ability to enter cells. But non-viral delivery systems such as lipid nanoparticles (LNPs) have also been successfully employed to deliver RNA-based therapeutics into cells.

A big advantage of using viral vectors for gene delivery is they are longer lasting than non-viral systems, states Dr. Rajvinder Karda, lecturer in gene therapy at University College London. Many of the rare diseases were aiming to tackle are severe and we need to achieve long-term gene expression for these treatments to be effective.

While improved technological prowess empowers the development of CRISPR-edited therapies, supply-chain and manufacturing hurdles still pose significant barriers to clinical and commercialization timelines. Watch this webinar to learn more about the state of CRISPR cell and gene therapies, challenges in CRISPR therapy manufacturing and a next-generation manufacturing facility.

Viral-vector gene therapies are either administered directly into the patients body (in vivo), or cells harvested from a patient are instead modified in the laboratory (ex vivo) and then reintroduced back into the body. Major challenges for in vivo gene delivery approaches are with the safe and efficient targeting of the therapeutic to the target cells and overcoming any potential immune responses to the vectors.

As well as getting the genetic material into the affected cells, we also need to try and limit it reaching other cells as expressing a gene in a cell where its not normally active could cause problems, explains Dr. Gerry McLachlan, group leader at the Roslin Institute in Edinburgh.

For example, the liver was identified as a major site of toxicity for an AAV-based gene therapy approved for treating spinal muscular atrophy (SMA), a type of motor neuron disease that affects people from a very young age.

Unfortunately, these viruses are leaky as theyre also going to organs that dont need therapy meaning you can get these off-target effects, says Karda. Theres still work to be done to develop and refine these technologies to make them more cell- and organ-specific.

It is also important to ensure the gene is expressed at the right level in the affected cells too high and it may cause side effects and too little may render the treatment ineffective. In a recent major advancement in the field, scientists developed a dimmer switch system Xon that enables gene expression to be precisely controlled through exposure to an orally delivered small molecule drug. This novel system offers an unprecedented opportunity to refine and tailor the application of gene therapies in humans.

Download this whitepaper to discover an electroporation system that resulted in CAR transfection efficiencies as high as 70% in primary human T cells, can avoid the potential risks associated with viral transduction and is able to produce CAR T cells at a sufficient scale for clinical and therapeutic applications.

In 1989, a team of researchers identified the gene that causes the chronic, life-limiting inherited disease cystic fibrosis (CF) the cystic fibrosis transmembrane conductance regulator (CFTR). This was the first ever disease-causing gene to be discovered marking a major milestone in the field of human genetics. In people with CF, mutations in the CFTR gene can result in no CTFR protein, or the protein being made incorrectly or at insufficient levels all of which lead to a cascade of problems that affect the lungs and other organs.

Our team focuses on developing gene therapies to treat respiratory diseases in particular, were aiming to deliver the CTFR gene into lung cells to treat CF patients, says McLachlan.

The results of the UK Respiratory Gene Therapy Consortiums most recent clinical trial showed that an inhaled non-viral CTFR gene therapy formulation led to improvements in patient lung function.

While this was encouraging, the effects were modest and we need to develop a more potent delivery vehicle, explains McLachlan. Weve also been working on a viral-based gene therapy using a lentiviral vector to introduce a healthy copy of the CTFR gene into cells of the lung.

Kardas team focuses on developing novel gene therapy and gene-editing treatments for incurable genetic diseases affecting the central and peripheral nervous system and Yez-Muoz is aiming to develop new treatments for rare neurodegenerative diseases that affect children, including SMA and ataxia telangiectasia (AT).

But a significant barrier for academic researchers around the world is accessing the dedicated resources, facilities and expertise required to scale up and work towards the clinical development and eventually the commercial production of gene and cell therapies. These challenges will need to be addressed and overcome if these important advancements are to successfully deliver their potentially life-changing benefits to patients.

Download this app note to discover how electron activated dissociation can obtain in-depth structural characterization of singly charged, ionizable lipids and related impurities, decrease risk of missing critical low abundance impurities and increase confidence in product quality assessment.

After many decades of effort, the future of gene and cell therapies is incredibly promising. A flurry of recent successes has led to the approval of several life-changing treatments for patients and many more products are in development.

Its no longer just about hope, but now its a reality with a growing number of rare diseases that can be effectively treated with these therapies, describes Yez-Muoz. We now need to think about how we can scale up these technologies to address the thousands of rare diseases that exist and even within these diseases, people will have different mutations, which will complicate matters even further.

But as more of these gene and cell-based therapies are approved, there is a growing urgency to address the challenge of equitable access to these innovative treatments around the world.

Gene therapies have the dubious honor of being the most expensive treatments ever and this isnt sustainable in the longer term, says Yez-Muoz. Just imagine being a parent and knowing there is an effective therapy but your child cant access it that would be absolutely devastating.

Read the rest here:
Cell and Gene Therapy: Rewriting the Future of Medicine - Technology Networks

DUBLIN--(BUSINESS WIRE)--The "Automated Cell Counters Market Forecast to 2028 - COVID-19 Impact and Global Analysis By Type and End User" report has been added to ResearchAndMarkets.com's offering.

The automated cell counters market is expected to grow from US$ 6,974.29 million in 2021 to US$ 10,365.95 million by 2028; it is estimated to grow at a CAGR of 5.9% from 2022 to 2028.

The report highlights trends prevailing in the market and factors driving the market growth. The market growth is attributed to the high prevalence of infectious and chronic diseases. Additionally, advancement in automated cell counters is likely to emerge as a significant trend in the market during the forecast period. However, the lack of a skilled workforce and the high instrument cost limit the market growth.

Chronic diseases are conditions that are present in an individual for one or more years, require ongoing medical attention, and can also result in limited daily activities. Chronic diseases are currently the major cause of death among adults in several countries. According to World Health Organization (WHO), 41 million people die yearly due to chronic diseases, equivalent to 71% of all deaths globally.

As per the Centers for Disease Control and Prevention (CDC), six in ten adults in the US have a chronic disease, and four in ten adults have two or more chronic diseases. According to Cancer Research UK, ~17 million new cases of cancer were detected worldwide in 2018. Further, in 2018, ~9.6 million deaths occurred due to cancer worldwide.

Infectious diseases are caused by infectious agents, such as viruses, bacteria, parasites, fungi, and toxic products. HIV is a major public health issue across the world. As per The Joint United Nations Programme on HIV/AIDS (UNAIDS), ~ 37.7 million people had HIV in 2020; out of these, 1.7 million were children aged 0-14 years, and 36 million were adults.

Further, over half of them (53%) were girls and women, and 1.5 million new HIV cases were globally reported in 2020. Similarly, hepatitis is inflammation of the liver caused by a viral infection. The five primary strains of hepatitis viruses are A, B, C, D, and E. According to WHO, ~58 million people have chronic hepatitis C, and ~1.5 million new infections occur every year.

According to WHO, tuberculosis (TB) is the thirteenth leading cause of death globally and the second leading infectious disease after COVID-19. Furthermore, 1.5 million deaths were caused by TB in 2020 (including 214,000 people affected by HIV). In 2020, the WHO estimated that 10 million people had TB, including 1.1 million children, 3.3 million women, and 5.6 million men. TB cases are present in all age groups and countries. Furthermore, 30 countries with high TB burdens accounted for 86% of new TB cases in 2020. Eight countries registered two-thirds of the total TB cases, with India at the forefront, followed by China, the Philippines, Indonesia, Nigeria, Pakistan, Bangladesh, and South Africa.

Diagnostics are essential in determining the direction of any medical treatment of infectious and chronic diseases. Cell counting is one of the methods that is used for the detection of such diseases. Therefore, the rising prevalence of infectious and chronic diseases across the globe is driving the growth of the automated cell counters market.

On the other hand, the lack of a skilled workforce and high instrument cost hinders the overall automated cell counters market growth. According to a WHO report, there is a drastic shortage of healthcare professionals or workers trained to use automated cell counter equipment. The ongoing research in pharmaceutical and biotechnology and the development of various drugs to treat diseases such as cancer, cardiovascular disorders, HIV/AIDS, etc.

With technological advancements in automated cell counters and a rise in application areas of the instrument, there has been a shift in usage of automated cell counters. The working of the automated cell counter is difficult, and knowledge of this instrument is highly important; hence, there is a demand for a skilled workforce. The preparation of a sample for such instruments is tedious work, and the consumables required during the procedure also need to be handled properly. Thus, a lack of a skilled workforce who can easily use these instruments is hampering the growth of the automated cell counters market.

Market Dynamics

Drivers

Restraints

Opportunities

Future Trends

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/aslixr

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Outlook on the Automated Cell Counters Global Market to 2028 - Use of Cell Counters in Personalized Medicine Presents Opportunities -...

JCR Pharmaceuticals Co., Ltd. and Sysmex Corporation announced that they have established a joint venture(hereafter the "joint venture") for carrying out research and development, manufacture and sales of cell-based regenerative medicine products including hematopoietic stem cells and other stem cells. In recent years, the significant potential of regenerative medicine and cell therapy have been established in particular in areas that have traditionally been difficult to address with conventional chemically synthesized low molecular weight drugs1 or biopharmaceuticals2, such as the restoration of tissues and functions lost as a result of aging, illness, autoimmune diseases, or cancer. In particular, research and development on the therapeutic application of stem cells including hematopoietic stem cells, mesenchymal stem cells, and iPS cells have generated significant attention. Since its inception, JCR has been engaged in the research, development, manufacturing and sales of pharmaceutical products using regenerative medicine, genetic engineering, and gene therapy technologies to advance therapies in the rare disease field. This is exemplified in the field of regenerative medicine, by the approval of TEMCELL HS Inj.3, the first allogeneic regenerativemedicine in Japan (Non-proprietary name: Human (allogeneic) bone marrow-derived mesenchymal stem cells) in February 2016 for the treatment of acute graft-versus-host disease (acute GVHD)4, a serious complication that develops after hematopoietic stem cell transplantation. In recent years, JCR has further streamlined and integrated its expertise around the establishment of groundbreaking medicines for the advancement of highly innovative medicines that could not be developed without such groundbreaking technologies. In the joint venture, the two companies aim to realize the social implementation of regenerative medicine and cell therapy by integrating JCR's expertise in developing, manufacturing and marketing regenerative medicine products, with Sysmex's expertise in quality control testing technology and knowledge of workflows efficiency using robotics technology, including IoT. AlliedCel Corporation, which is the corporate name of the joint venture following prior discussions regarding the alliance both companies, was established on October 3, 2022. The joint venture will advance programs of the potential for technology development and commercialization, including the project currently being promoted by both companies using hematopoietic stem cell proliferation technology. The name AlliedCel stands for the joint venture's aspiration to integrate knowledge and expertise from a broad set of collaborators and stakeholders including business partners, patients and their families, with the united goal of unleashing the power of cells in supporting patients in their needfor life-changing therapies. Through the research and development of regenerative medicineproducts using diverse cells such as stem cells, AlliedCel aims to provide appropriate treatmentoptions to patients and improve their prognosis.

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Jcr Pharmaceuticals Co., Ltd. and Sysmex Establish A Joint Venture in the Field of Regenerative Medicine and Cell Therapy - Marketscreener.com

Biopharma focuses on streamlining biomanufacturing and supply chain issues to drive uptake of cell and gene therapies.

Cell and gene therapies (CGTs) offer significant advances in patient care by helping to treat or potentially cure a range of conditions that have been untouched by small molecule and biologic agents. Over the past two decades, more than 20 CGTs have been approved by FDA in the United States and many of these one-time treatments cost between US$375,00 and US$2 million a shot (1). Given the high financial outlay and patient expectations of these life-saving therapies, it is essential that manufacturers provide integrated services across the whole of the supply chain to ensure efficient biomanufacturing processes and seamless logistics to reduce barriers to uptake.

The following looks at the who, what, when, and why of biomanufacturing and logistics in CGTs in the bio/pharmaceutical industry in more detail.

According to market research, the global gene therapy market will reach US$9.0 billion by 2027 due to favorable reimbursement policies and guidelines, product approvals and fast-track designations, growing demand for chimeric antigen receptor (CAR) T cell-based gene therapies, and improvements in RNA, DNA, and oncolytic viral vectors (1).

In 2020, CGT manufacturers attracted approximately US$2.3 billion in investment funding (1). Key players in the CGT market include Amgen, Bristol-Myers Squibb Company, Dendreon, Gilead Sciences, Novartis, Organogenesis, Roche (Spark Therapeutics), Smith Nephew, and Vericel. In recent years, growth in the CGT market has fueled some high-profile mergers and acquisitions including bluebird bio/BioMarin, Celgene/Juno Therapeutics, Gilead Sciences/Kite, Novartis/AveXis and the CDMO CELLforCURE, Roche/Spark Therapeutics, and Smith & Nephew/Osiris Therapeutics.

Many bio/pharma companies are re-considering their commercialization strategies and have re-invested in R&D to standardize vector productions and purification, implement forward engineering techniques in cell therapies, and improve cryopreservation of cellular samples as well as exploring the development of off-the-shelf allogeneic cell solutions (2).

The successful development of CGTs has highlighted major bottlenecks in the manufacturing facilities, and at times, a shortage of raw materials (3). Pharma companies are now taking a close look at their internal capabilities and either investing in their own manufacturing facilities or outsourcing to contract development and manufacturing organizations (CDMOs) or contract manufacturing organizations (CMOs) to expand their manufacturing abilities (4). Recently, several CDMOsSamsung Biologics, Fujifilm Diosynth, Boehringer Ingelheim, and Lonzahave all expanded their biomanufacturing facilities to meet demand (5).

A major challenge for CGT manufacturers is the seamless delivery of advanced therapies. There is no room for error. If manufacturers cannot deliver the CGT therapy to the patient with ease, the efficacy of the product becomes obsolete. Many of these therapies are not off-the-shelf solutions and therefore require timely delivery and must be maintained at precise temperatures to remain viable. Thus, manufacturers must not only conform to regulations, but they must also put in place logistical processes and contingency plans to optimize tracking, packaging, cold storage, and transportation through the products journey. Time is of the essence, and several manufacturers have failed to meet patient demands, which have significant impacts on the applicability of these agents.

Several CAR T-cell therapies have now been approved; however, research indicates that a fifth of cancer patients who are eligible for CAR-T therapies pass away while waiting for a manufacturing slot (6). Initially, the manufacture of many of these autologous products took around a month, but certain agents can now be produced in fewer than two weeks (7). Companies are exploring new ways to reduce vein-to-vein time (collection and reinfusion) through the development of more advanced gene-transfer tools with CARs (such as transposon, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) among others, and the use of centralized organization with standardized apheresis centers (5). Others are exploring the use of the of allogeneic stem cells including Regen Biopharma, Escape Therapeutics, Lonza, Pluristem Therapeutics, and ViaCord (7).

Several gene therapies have also been approved, mainly in the treatment of rare disease (8). Many companies are evaluating novel gene therapy vectors to increase levels of gene expression/protein productions, reduce immunogenicity and improve durability including Astellas Gene Therapies, Bayer, ArrowHead Pharmaceuticals, Bayer, Bluebird Bio, Intellia Therapeutics, Kystal Biotech, MeiraGTx, Regenxbio, Roche, Rocket Pharmaceuticals, Sangamo Therapeutics, Vertex Pharmaceuticals, Verve Therapeutics, and Voyager Therapeutics (8).

While many biopharma companies have established their own in-house CGT good manufacturing practice (GMP) operation capabilities, others are looking to decentralize manufacturing and improve distribution by relying on external contracts with CDMOs and CMOs such as CELLforCURE, CCRM, Cell Therapies Pty Ltd (CTPL), Cellular Therapeutics Ltd (CTL), Eufets GmbH, Gravitas Biomanufacturing, Hitachi Chemical Advances Therapeutic Solutions, Lonza, MasTHerCell, MEDINET Co., Takara Bio, and XuXi PharmaTech (6, 9, 10).

The top 50 gene therapy start-up companies have attracted more than $11.6 billion in funds in recent years, with the top 10 companies generating US$5.3 billion in series A to D funding rounds (10). US-based Sana Biotechnology leads the field garnering US$700 million to develop scalable manufacturing for genetically engineered cells and its pipeline program, which include CAR-T cell-based therapies in oncology and CNS (Central Nervous System) disorders (11). In second place, Editas Medicine attracted $656.6 million to develop CRISPR nuclease gene editing technologies to develop gene therapies for rare disorders (12).

Overall, CGTs have attracted the pharma industrys attention as they provide an alternative route to target diseases that are poorly served by pharmaceutical and/or medical interventions, such as rare and orphan diseases. Private investors continue to pour money into this sector because a single shot has the potential to bring long-lasting clinical benefits to patients (13). In addition, regulators have approved several products and put in place fast track designation to speed up patient access to these life-saving medicines. Furthermore, healthcare providers have established reimbursement policies and manufacturers have negotiated value- and outcome-based contracts to reduce barriers to access to these premium priced products

On the downside, the manufacture of CGTs is labor intensive and expensive with manufacturing accounting for approximately 25% of operating expenses, plus there is still significant variation in the amount of product produced. On the medical side, many patients may not be suitable candidates for CGTs or not produce durable response due to pre-exposure to the viral vector, poor gene expression, and/or the development of immunogenicity due to pre-exposure to viral vectors. Those that can receive these therapies may suffer infusion site reactions, and unique adverse events such as cytokine release syndrome and neurological problems both of which can be fatal if not treated promptly (14).

Despite the considerable advances that have been made in the CGT field to date, there is still much work needed to enhance the durability of responses, increase biomanufacturing efficiencies and consistency and to implement a seamless supply chain that can ensure these agents are accessible, cost-effective, and a sustainable option to those in need.

Cleo Bern Hartley is a pharma consultant, former pharma analyst, and research scientist.

BioPharm InternationalVol. 35, No. 10October 2022Pages: 4951

When referring to this article, please cite it as C.B. Hartley, "Growth in Cell and Gene Therapy Market," BioPharm International 35 (10) 4951 (2022).

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Growth in Cell and Gene Therapy Market - BioPharm International

Stanford University researchers have discovered a rapid and sustainable way to synthetically produce a promising cancer-fighting compound right in the lab. The compounds availability has been limited because its only currently known natural source is a single plant species that grows solely in a small rainforest region of Northeastern Australia.

PhD students Edward Njoo, David Fanelli, Zach Gentry, and Owen McAteer. These researchers achieved the synthesis of the cancer-fighting compound EBC-46. (Image credit: Paul Wender)

The compound, designated EBC-46 and technically called tigilanol tiglate, works by promoting a localized immune response against tumors. The response breaks apart the tumors blood vessels and ultimately kills its cancerous cells. EBC-46 recently entered into human clinical trials following its extremely high success rate in treating a kind of cancer in dogs.

Given its complex structure, however, EBC-46 had appeared synthetically inaccessible, meaning no plausible path seemed to exist for producing it practically in a laboratory. However, thanks to a clever process, the Stanford researchers demonstrated for the first time how to chemically transform an abundant, plant-based starting material into EBC-46.

As a bonus, this process can produce EBC-46 analogs compounds that are chemically similar, but which could prove even more effective and potentially treat a surprisingly wide range of other serious maladies. These diseases, which include AIDS, multiple sclerosis, and Alzheimers disease, all share biological pathways impacted by EBC-46s target, a key enzyme called protein kinase C, or PKC.

We are very excited to report the first scalable synthesis of EBC-46, said Paul Wender, the Francis W. Bergstrom Professor in the School of Humanities and Sciences, professor of chemistry and, by courtesy, of chemical and systems biology at Stanford, and corresponding author of a study describing the results in the journal Nature Chemistry. Being able to make EBC-46 in the lab really opens up tremendous research and clinical opportunities.

Co-authors of the study are Zachary Gentry, David Fanelli, Owen McAteer, and Edward Njoo, all of whom are PhD students in Wenders lab, along with former member Quang Luu-Nguyen.

Wender conveyed the immense satisfaction the research team felt over the EBC-46 synthesis breakthrough. If you were to have visited the lab the first few weeks after they succeeded, said Wender, you wouldve seen my stellar colleagues smiling from ear to ear. They were able to do something many people had considered impossible.

Tigilanol tiglate initially turned up through an automated drug candidate screening process by QBiotics, an Australian company. In nature, the compound appears in the seeds of the pink fruit of the blushwood tree, Fontainea picrosperma. Marsupials such as musky rat-kangaroos that eat blushwood fruit avoid the tigilanol tiglate-rich seeds, which when ingested trigger vomiting and diarrhea.

Injecting far smaller doses of EBC-46 directly into some solid tumors modifies the cellular signaling by PKC. Specifically, EBC-46 is proposed to activate certain forms of PKC, which in turn influence the activity of various proteins in the cancerous cells, attracting an immune response by the hosts body. The resulting inflammation makes the tumors vasculature, or blood vessels, leaky, and this hemorrhaging causes the tumorous growth to die. In the case of external, cutaneous malignancies, the tumors scab up and fall off, and ways of delivering EBC-46 to internal tumors are being investigated.

In 2020, both the European Medicines Agency and the Food and Drug Administration in the United States approved an EBC-46based medication, sold under the brand name Stelfonta, to treat mast cell cancer, the most common skin tumors in dogs. A study showed a 75% cure rate after a single injection and an 88% rate following a second dose. Clinical trials have since commenced for skin, head and neck, and soft tissue cancers in humans.

Based on these emerging research and clinical needs coupled with the source seeds geographical limitations, scientists have considered setting up special plantations for blushwood trees. But doing so presents a host of issues. For starters, the trees require pollination, meaning the right sort of pollinating animals must be on hand, plus trees must be planted in appropriate densities and distances to aid pollination. Furthermore, seasonal and climate variations affect the trees, along with pathogens. Setting aside plots for blushwood trees further poses land use problems.

For sustainable, reliable production of EBC-46 in the quantities we need, Wender said, we really need to go the synthetic route.

A good starting point for making EBC-46, Wender and colleagues realized, is the plant-derived compound phorbol. More than 7,000 plant species produce phorbol derivatives worldwide and phorbol-rich seeds are commercially inexpensive. The researchers selected Croton tiglium, commonly known as purging croton, an herb used in traditional Chinese medicine.

The first step in preparing EBC-46, Wender explains, jibes with an everyday experience. You buy a sack of these seeds, and its not unlike making coffee in the morning, said Wender. You grind up the seeds and run some hot solvent through them to extract the active ingredient, in this case a phorbol-rich oil.

After processing the oil to yield phorbol, the researchers then had to figure out how to overcome the previously insurmountable challenge of bedecking a part of the molecule, called the B ring, with carefully placed oxygen atoms. This is required to enable EBC-46 to interact with PKC and modify the enzymes activity in cells.

To guide their chemical and biological studies, the researchers relied on instrumentation at the Stanford Neuroscience Microscopy Service, the Stanford Cancer Institute Proteomics/Mass Spectrometry Shared Resource, and the Stanford Sherlock cluster for computer modeling.

With this guidance, the team succeeded in adding extra oxygen atoms to phorbols B ring, first via a so-called ene (pronounced een) reaction conducted under flow conditions, where reactants mix as they run together through tubing. The team then introduced other B ring groups in a stepwise, controlled manner to obtain the desired spatial arrangements of the atoms. In total, only four to six steps were required to obtain analogs of EBC-46 and a dozen steps to reach EBC-46 itself.

Wender hopes that the far broader availability of EBC-46 and its PKC-influencing cousin compounds afforded by this breakthrough approach will accelerate research into potentially revolutionary new treatments.

As we learn more and more about how cells function, were learning more about how we can control that functionality, said Wender. That control of functionality is particularly important in dealing with cells that go rogue in diseases ranging from cancer to Alzheimers.

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Breakthrough in production of cancer-treating drug - Stanford University News

ZUG, Switzerland and BOSTON, Sept. 28, 2022 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to CTX130, the Companys wholly-owned allogeneic CAR T cell therapy targeting CD70, for the treatment of Mycosis Fungoides and Szary Syndrome (MF/SS).

The RMAT designation is an important milestone for the CTX130 program that recognizes the transformative potential of our cell therapy in patients with T-cell lymphomas based upon encouraging clinical data to date, said Phuong Khanh (P.K.) Morrow, M.D., FACP, Chief Medical Officer of CRISPR Therapeutics. "We continue to work with a sense of urgency to bring our broad portfolio of allogeneic cell therapies to patients in need.

Established under the 21st Century Cures Act, RMAT designation is a dedicated program designed to expedite the drug development and review processes for promising pipeline products, including genetic therapies. A regenerative medicine therapy is eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug or therapy has the potential to address unmet medical needs for such disease or condition. Similar to Breakthrough Therapy designation, RMAT designation provides the benefits of intensive FDA guidance on efficient drug development, including the ability for early interactions with FDA to discuss surrogate or intermediate endpoints, potential ways to support accelerated approval and satisfy post-approval requirements, potential priority review of the biologics license application (BLA) and other opportunities to expedite development and review.

About CTX130 and COBALT TrialsCTX130, a wholly-owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR T investigational therapy targeting Cluster of Differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX130 is being investigated in two ongoing independent Phase 1 single-arm, multi-center, open-label clinical trials that are designed to assess the safety and efficacy of several dose levels of CTX130 in adult patients. The COBALT-LYM trial is evaluating the safety and efficacy of CTX130 for the treatment of relapsed or refractory T or B cell malignancies. The COBALT-RCC trial is evaluating the safety and efficacy of CTX130 for the treatment of relapsed or refractory renal cell carcinoma. CTX130 has received Orphan Drug and Regenerative Medicine Advanced Therapy designations from the FDA.

About CRISPR TherapeuticsCRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic partnerships with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts, and business offices in San Francisco, California and London, United Kingdom. For more information, please visit http://www.crisprtx.com.

CRISPR Forward-Looking StatementThis press release may contain a number of forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements made by Dr. Morrow in this press release, as well as regarding CRISPR Therapeutics expectations about any or all of the following: (i) the status of clinical trials and discussions with regulatory authorities related to product candidates under development by CRISPR Therapeutics including, without limitation, expectations regarding the benefits of RMAT designation; and (ii) the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies. Without limiting the foregoing, the words believes, anticipates, plans, expects and similar expressions are intended to identify forward-looking statements. You are cautioned that forward-looking statements are inherently uncertain. Although CRISPR Therapeutics believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: the potential for initial and preliminary data from any clinical trial and initial data from a limited number of patients not to be indicative of final trial results; the potential that clinical trial results may not be favorable; potential impacts due to the coronavirus pandemic, such as the timing and progress of clinical trials; that future competitive or other market factors may adversely affect the commercial potential for CRISPR Therapeutics product candidates; uncertainties regarding the intellectual property protection for CRISPR Therapeutics technology and intellectual property belonging to third parties, and the outcome of proceedings (such as an interference, an opposition or a similar proceeding) involving all or any portion of such intellectual property; and those risks and uncertainties described under the heading "Risk Factors" in CRISPR Therapeutics most recent annual report on Form 10-K, quarterly report on Form 10-Q and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission, which are available on the SEC's website at http://www.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. CRISPR Therapeutics disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.

CRISPR THERAPEUTICS standard character mark and design logo, CTX130 and COBALT are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners.

Investor Contact:Susan Kim+1-617-307-7503susan.kim@crisprtx.com

Media Contact:Rachel Eides+1-617-315-4493rachel.eides@crisprtx.com

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CRISPR Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to CTX130 for the Treatment of Cutaneous T-Cell...

Mary Munson, PhD

Mary Munson, PhD, professor of biochemistry & molecular biotechnology and vice chair of diversity for the department, is one of 22 scientists named a fellow by the American Society for Cell Biology for 2022.

Election as a fellow is an honor bestowed upon society members by their peers. Fellows are recognized for their lifetime achievement in advancing cell biology, meritorious efforts to advance cell biology and its applications, and for their service to the society.

Dr. Munson will be among the new cohort of fellows to be formally recognized in Washington, D.C., in December at Cell Bio 2022, the joint meeting of the American Society for Cell Biology and the European Molecular Biology Organization.

I am honored to be recognized in this years cohort and to join such a distinguished group of cell biologists, said Munson.

An expert in the mechanistic basis for regulation of spatial and temporal membrane trafficking, Munson is interested in understanding how cargo arrives at the correct location at the right time throughout the cell and is either released to or internalized from the extracellular space. The Munson Lab aims to answer questions about membrane trafficking through a multifaceted approach that combines biochemical, structural and biophysical techniques with yeast and mammalian genetics, microscopy and cell biological methods.

Munson joined UMass Chan Medical School in 2001. Prior to joining the faculty, she was a postdoctoral fellow in the department of molecular biology at Princeton University, where she was awarded American Heart Association and National Institutes of Health fellowships. She was a double major in chemistry and biology at Washington University (St. Louis) and received her PhD from Yale University in molecular biophysics and biochemistry. In 2015, Munson was awarded the inaugural Bassick Family Worcester Foundation Award.

Since joining UMass Chan, Munson has been closely involved with teaching and curriculum development for the Morningside Graduate School of Biomedical Sciences and has been recognized by the institution several times for her outstanding contributions to curriculum development and student mentoring. She is the faculty advisor for the UMass Chan student chapter of the Society for Advancement of Chicanos/Hispanics and Native Americans in Science. She is a leader of the diversity action committee in the Department of Biochemistry &Molecular Biotechnology and leads the new Morningside Graduate School of Biomedical Sciences Faculty Focused on Inclusive Excellence committee, focused on engaging and educating faculty to promote diversity, equity and inclusion on campus.

She is the co-chair of the American Society for Cell Biologys Women in Cell Biology committee and a co-investigator of its AMP MOSAIC program. She recently became a trained facilitator for Entering Mentoring, a program sponsored by the Center for the Improvement of Mentored Experiences in Research to enable strong and supportive scientific mentors.

Munson joins Gregory J. Pazour, PhD, professor of molecular medicine; Thoru Pederson, PhD, the Vitold Arnett Professor of Cell Biology and professor of biochemistry & molecular biotechnology; and George B. Witman, PhD, professor emeritus of radiology, in being named fellows of the American Society for Cell Biology.

Related UMass Chan News storiesAt MLK tribute,Mary Munsonrecognized for commitment to diversity and inclusion in science fieldUMMS researcher co-directs project to enhance diversity in biomedical sciences workforce.Thoru Pederson named fellow of theAmerican Society for Cell BiologyGregory Pazour elected fellow of theAmerican Society for Cell Biology

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Mary Munson elected fellow of the American Society for Cell Biology - UMass Medical School