Category Archives: Cell Therapy

For cell therapy to become mainstream, important issues such as management of risk and quality control need to be addressed, argues Duncan Borthwick, Global Marketing Manager at cell therapy manufacturing firm Solentim.

Research and development of cell therapies, along with other advanced medicines like gene therapies, has increased exponentially over the last few years.

According to the Alliance for Regenerative Medicine,as of June this year there were over 2,000 ongoing clinical trials of cell therapies around the world. Of these, 541 were at phase III.

Its absolutely boom time for cell therapy, Borthwick told me, adding that the field has changed enormously in recent years. Its just unimaginably different. And not only its applications, but also the robustness of the methodologies. You speak to some of the researchers and they say two years ago, we couldnt get these cells to grow.

With an increased presence in medicine comes increased scrutiny. Following the appearance of adverts for cell therapies to treat or cure serious diseases in early 2020, the EMA released a statement warning patients against using unregulated cell therapies due to safety concerns.

Similar warnings have also been distributed in the US. Cell therapy developers and clinics offering such therapies were given a break by the FDA in 2017 and told to collect evidence to see if they needed to submit an investigational new drug or marketing application. That period of grace ran out in May this year and the FDA is now enforcing stricter regulations on people offering such therapies.

Unregulated cell-based therapies are a great concern to everybody, says Borthwick. In this context, tighter regulatory control of cell therapies can be beneficial for the industry.

Being able to designate gene therapies and somatic cell therapies in tissue-engineered products under a category is really, really helpful. It sets a new kind of cornerstone for that regulatory framework and also a mechanism by which companies can approach the regulator in terms of clinical trials, says Borthwick.

Although many cell therapies do go through a rigorous development process, it is still a relatively new field. Risk management and quality control can be difficult to navigate for new startups looking to take a cell therapy to market.

One of the many challenges of cell therapy is to make robust control mechanisms by which young and old companies can build a path to develop clinical products, which are going to help peoples lives, explains Borthwick.

A problem with any therapy based on live components is that controlling variation between different batches can be a problem.

If youre trying to control the risk to humans, you control the risk in production, whats called a control strategy, says Borthwick. One of the key ways you can do that is to say, instead of starting with a big pool of cells that are all different, lets take it down into individual cells, pick a good one and make that into a master cell bank.

This has historically been a challenge, as the technology was not advanced enough, says Borthwick. Researchers reduced the volume of cells, carefully pipetted it out, and hoped that some contained single cells that could be the parent of a new cell line.

To address this problem, Solentims founders created imaging processes that could take away the doubt around whether or not a single cell was present when starting a new cell line. The company now covers the whole cell line production process and has expanded into seeding and growth methods.

Solentim has been working closely with researchers and therapy developers across the industry, as well as regulators such as the EMA and FDA, on getting the different steps right.

When you put in a proposal for human treatments, an IND submission, you dont pass the IND submission, you just dont get negative comments at that time. Theres an ongoing review process, explains Borthwick.

Its a very risk-averse community. Rightly so, because if you get it wrong, youre going to get a nasty letter from the FDA. But moreover, you might be developing this for five years. If you dont get this bit right, the regulator is going to come back and say thats too much of a risk to bring to human trials. So, its really important to get it right.

Once a good quality cell line has been created, Borthwick says another important point to consider for cell therapy developers is the scalability and continuity of the process.

You cant wait until you find yourself in production before scrambling to put together a quality process. And theres so much to be gained from starting to think early about that proportional approach to quality.

For instance, how many other providers are involved in the process and how well do you understand their processes? Theres a massive thing about single vendor use going on. If I can understand one vendor really well, then thats so much easier to manage than 20.

The important thing is to find methods that work and then are scalable in terms of throughput. Once youre moving from research to production, can you scale that whole story of risk analysis, paperwork, and regulation? Ultimately, it makes the whole thing so much easier.

Borthwick encourages young startups or academic spinouts that are trying to move from an academic laboratory set up to a large-scale therapy production line to think seriously about this and to question all their initial processes. For example, some cell growth reagents are fine to use in the lab on a small scale, but wont work when scaled up.

Theres many which have animal products in them, which then present massive challenges as you approach clinical trials. There are others which cannot have GMP certification, and theres others that just wont work on high-throughput automation, for instance, he says.

Sometimes you need to stop and think a little bit. Put in place good practices now That might be staff or processes, get people involved at an early stage, because it is going to give you massive time savings later on. Dont be terrified by the world of regulation and risk. Theres a lot of good people out there.

Having an industrial scale-up process that maintains quality and reduces therapy variation will only become more important for companies to succeed in the long run.

We are contacted every week by some company we havent heard of that are moving into the space, says Borthwick, who adds that neighbouring markets, such as cultured meat producers, are also carefully observing cell therapy developers to try and learn from their processes and methodology about how to maintain quality and reduce risks.

Both the FDA and EMA have been learning about advanced therapies and developing the best ways to regulate them over the last few years, but are now becoming more familiar with the area. Borthwick advocates good communication and discussion with the local regulatory agencies when trying to bring a product to market.

One of our collaborators said that their greatest fear is that the regulator will never OK their products, because they wont be able to see if theyve managed risk appropriately. Its up to us to communicate that approach effectively from an early stage to the regulator, because we all want this to work.

Read more from the original source:
Thinking About Risk Early on Is Key for Cell Therapy Success - Labiotech.eu

Caron A. Jacobson, MD, MMSC, highlights data supporting the use of CAR T-cell therapy in patients with indolent lymphoma.

Those with B-cell histology have derived positive clinical benefit from treatment with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy, with those with indolent B-cell non-Hodgkin lymphoma achieving a high rate of durable remission. Although early data from first-in-human research indicated that this treatment appears promising, longer follow up is necessary in order to confirm whether the responses translate to cures in patients with these indolent, difficult-to-treat diseases.1

Caron A. Jacobson, MD, MMSC, medical director, Immune Effector Cell Therapy Program and senior physician at Dana-Farber Cancer Institute in Boston, Massachusetts, discussed results from the ZUMA-5 trial (NCT03105336), provided a comparison between ZUMA-5 and the SCHOLAR-5 trials,2 and interim results from the ELARA study (NCT03568461) in a presentation at the Society of Hematologic Oncology 2021 Annual Meeting on September 10, 2021.

ZUMA-5 evaluated axicabtagene ciloleucel (axi-cel; Yescarta) in 124 patients with follicular lymphoma (FL) and 22 patients with marginal zone lymphoma (MZL) who had undergone 3 lines of prior therapy. The primary end point was overall response rate (ORR), and key secondary end points were complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and incidence of adverse events (AEs).

These were a group of patients at high-risk, with the majority [46.5%] having FLIPI scores greater than 3, Jacobson, an assistant professor of medicine at Harvard Medical School, said. In addition, many patients (54.1%) were classified as POD24, ie, having progression of disease within 24 months of receiving their first anti-CD20 monoclonal antibodycontaining therapy.

In ZUMA-5, ORR was 92% with a CR rate of 76%. For patients with FL, after 12 months of follow up, the ORR was 94% (n = 84) with a CR of 80%. For patients with MZL, the ORR was 85% (n = 20) with a CR rate of 60% (n = 12). It is notable that 52% of patients who had had an initial partial response at first tumor restaging, went on to have a CR after a median of 2.2 months of follow-up, Jacobson said in her presentation.

In patients with FL, median DFS, PFS, and OS have not been reached; among patients who had responded at a median follow-up of 18 months, 78% were maintaining their response. Jacobson said the MZL survival curves were quite immature because patients only needed one month of follow-up to be included in the efficacy analysis. We are awaiting longer-term follow-up for this cohort, Jacobson noted.

When outcomes by POD24 were reviewed, patients with FL and MZL with POD24 had a lower CR rate and a shorter DOR and PFS than those without POD24. This was most notable in the MZL cohort, where only 58% of patients had a CR in the POD24 group compared with 75% and the median DOR was 11.1 months. Median PFS was 9.2 months for patients with POD24 compared with not reached for both end points for patients with MZL without POD24, Jacobson explained.

The safety profile appeared more favorable than that observed with axi-cel in patients with diffuse large B-cell lymphoma (DLBCL) with only 7% of patients having grade 3 or greater cytokine release syndrome (CRS) and 19% of patients with grade 3 or greater neurologic events. Also, the median time to onset of CRS was later in FL and MZL at 4 days, compared with DLBCL at 2 days, according to findings from the ZUMA-1 study (NCT02348216).

Results from the SCHOLAR-5 study were presented at the 2021 European Hematology Association Meeting (EHA2021).2 This was a retrospective meta-analysis comparing clinical outcomes from the updated 18-month ZUMA-5 study to a matched sample from the SCHOLAR-5 study. Data from the pivotal DELTA trial (NCT01282424) evaluating idelalisib (Zydelig) was included in the SCHOLAR-5 cohort. Eighty-five patients in the SCHOLAR-5 study and 86 patients in ZUMA-5 were evaluable after propensity score weighing was applied to the cohorts.

In third-line or higher, the ORR was 49.9% in SCHOLAR-5 compared with 94.2% for an OR of 16.2 (95% CI, 5.6-46.9). The median PFS and OS were not reached in ZUMA-5 and in SCHOLAR-5 were 12.7 months and 59.8 months, respectively. The analysis revealed a statistically significant improvement in both overall response rate from 49.9% to 94.2%, and a complete response rate from 29.9% to 79.2%, Jacobson said. This translates to an improvement in PFS, time-to-next treatment, and a statistically significant improvement in overall survival that was seen even within the first 3 years of follow-up.

Another study that evaluates CD19-directed CAR T cell therapy in follicular therapy is the ELARA study.3 The study evaluated tisagenlecleucel (Kymriah) in relapsed FL in patients who are in the third line setting and beyond. Investigators reported a complete response rate of 66%, with an ORR of 86% and a median follow-up of 11 months. Jacobson noted that a high proportion of patients maintained their response and that the PFS and OS curves were like those presented in ZUMA-5.

Regarding safety, Jacobson said the toxicity profile for tisagenlecleucel in FL was improved over the toxicity for the agent in patients with DLBCL and was better than the safety profile of axicabtagene ciloleucel. Investigators reported that 48.5% of patients had any grade CRS and no patients had grade 3 or higher CRS. In terms of immune cellassociated neurologic syndrome (ICANS), 9.3% of patients had any grade ICANS and 1% of patients had grade 3 or higher ICANS.3

According to Jacobson, other ongoing studies include ZUMA-5, explores axi-cel in patients with marginal zone lymphoma, the ongoing ELARA study, and the TRANSCEND study (NCT02631044), which evaluates lisocabtagene maraleucel (Breyanzi) in follicular lymphoma. Further, phase 1/2 studies that explore new agents include both allogeneic and natural killer CAR T-cells, as well as dual antigen targeting CARs that involve patients with indolent lymphomas.

We are hopeful that these emerging therapies will change the course of these cancers and provide curative therapy for our patients, concluded Jacobson.

Read more from the original source:
The Benefit of CAR T-Cell Therapy in Indolent Lymphoma - Cancer Network

DUBLIN--(BUSINESS WIRE)--The "Cell Therapy Consumables Market by Type of Consumable, Type of Cell Therapy, Scale of Operation, Type of End-User and Key Geographical Regions: Industry Trends and Global Forecasts, 2021 - 2031" report has been added to ResearchAndMarkets.com's offering.

This report features an extensive study on the consumable providers within the cell therapy industry. The study also includes an elaborate discussion on the future potential of this evolving market.

According to the US Food and Drug Administration (FDA), there has been an evident increase in the number of cell and gene therapy products being evaluated in early phases of development. This can further be validated by the observed upsurge in the number of investigational new drug (IND) applications. In fact, more than 800 IND applications have been filed for ongoing clinical studies, indicating remarkable scientific progress and therapeutic promise of these breakthrough drug candidates. However, manufacturing of cell therapies is a complex and capital-intensive process fraught with a wide range of challenges. Some of the key concerns of contemporary innovators include raw material supply constraints, current facility limitations, high cost of ancillary materials (buffers, growth factors and media) used in upstream processes, regulatory and compliance-related issues, and inconsistencies related to quality attributes of the final product. Further, the onset of recent COVID-19 pandemic has created additional challenges for therapy developers, in terms of procuring the required raw materials, by disrupting well-established supply chains.

Recent reports indicate that the global demand for human serum albumin (a key component of cell culture media for use in a multitude of therapeutic and emerging biotech areas) has increased at an annual rate of 10%-15%. On the contrary, the use of animal components is highly disregarded by the US FDA, European Medicines Agency (EMA), and other regulatory bodies on the grounds that they pose an undesirable risk of transmitting infectious agents, such as prions (mad cow disease) and virus (HIV), as well as enable high batch-to-batch variation. Consequently, serum-free and xeno-free media have proven to be a promising alternative to serum derived components. In order to produce quality cellular therapies, several drug developers prefer to rely on third-party service providers for the supply of raw materials, such as cell culture medium, cell isolation kits and cell separation reagents.

Presently, over 60 service providers are actively engaged in providing consumable/raw material products for the production of cell therapies. The current consolidated market landscape is primarily dominated by the presence of large players, capturing a substantial proportion of the market share. In the recent past, many of the aforementioned service providers have also forged strategic alliances and/or acquired other players, in order to further enhance their respective service offerings. Given that the demand for cell therapies is indubitably rising, the corresponding opportunity for cell therapy consumable service providers is expected to witness steady growth, over the next decade.

Key Questions Answered

Key Topics Covered:

1. PREFACE

2. EXECUTIVE SUMMARY

3. INTRODUCTION

4. MARKET LANDSCAPE

5. COMPANY COMPETITIVENESS ANALYSIS

6. BRAND POSITIONING OF KEY INDUSTRY PLAYERS

7. COMPANY PROFILES

7.1. Chapter Overview

7.2. Miltenyi Biotec

7.2.1. Company Overview

7.2.2. Product Portfolio

7.2.3. Recent Developments and Future Outlook

7.3. STEMCELL Technologies

7.4. Bio-Techne

7.5. Irvine Scientific

7.6. Thermo Fisher Scientific

7.7. Sartorius

7.8. BD Biosciences

7.9. Lonza

7.10. CellGenix

7.11. Corning

8. RECENT DEVELOPMENTS AND INITIATIVES

9. LIKELY PARTNER ANALYSIS FOR CELL THERAPY CONSUMABLE PROVIDERS

10. DEMAND ANALYSIS

11. MARKET FORECAST AND OPPORTUNITY ANALYSIS

12. UPCOMING TRENDS AND FUTURE GROWTH OPPORTUNITIES

13. IMPACT OF COVID-19 ON CELL THERAPY CONSUMABLES MARKET

14. CONCLUDING REMARKS

15. INTERVIEW TRANSCRIPTS

16. APPENDIX I: TABULATED DATA

17. APPENDIX II: LIST OF COMPANIES AND ORGANIZATIONS

For more information about this report visit https://www.researchandmarkets.com/r/17t5mu

Continued here:
Global Cell Therapy Consumables Market (2021 to 2031) - by Type of Consumable, Type of Cell Therapy, Scale of Operation, Type of End-User and Key...

The CAR T-cell therapy may provide another therapy option for patients with large B-cell lymphoma.

CTX110, an allogeneic chimeric antigen receptor (CAR) T-cell therapy for the treatment of relapsed or refractory CD19-positive B-cell malignancies, is well tolerated across a variety of dosing levels, according to results of the phase 1 CARBON (NCT04035434) released by CRISPR Therapeutics.1

We are excited to share positive data from our CARBON trial, which show that CTX110 could offer patients with large B-cell lymphomas an immediately available off-the-shelf therapy with efficacy similar to autologous CAR T and a differentiated safety profile, said Samarth Kulkarni, PhD, chief executive officer of CRISPR Therapeutics, in a press release. Furthermore, we have the potential to improve upon already observed efficacy with a consolidation dosing strategy. Based on these encouraging results, we are planning to expand CARBON into a potentially registrational trial in the first quarter of 2022.

The phase 1 CARBON study has an estimated enrollment of 143 participants and an estimated study completion date of August 2026. The primary end point of the dose escalation portion is the rate of adverse events (AEs). The primary end point of the dose expansion cohort is objective response rate (ORR). Secondary end points include duration of response, duration of clinical benefit, and progression-free survival.2

1

During the study, patients received a single transfusion of CTX110 following 3 days of a standard lymphodepletion regimen. The regimen contained fludarabine 30mg/m2 a day and cyclophosphamide 500mg/m2 a day. At disease progression, patients were eligible for redosing.

At the August 26, 2021 data cutoff, 30 patients with large B-cell lymphoma (LBCL) had been enrolled, 26 of which had received the agent with at least 28 days of follow-up. Only patients with at least 28 days of follow-up were included in the analysis.

The ORR was 58% and the complete response rate (CR) was 38% in LBCL with a single dose of the agent at dose level 2 and above. The 6-month CR rate was 21%, and the longest response was still ongoing at 18 months after initial infusion.

In terms of safety, no cases of graft versus host disease and no infusion reactions were reported. Only grade 1 or 2 cytokine release syndrome was observed. Other AEs included infections such as 1 case of pseudomonal sepsis and one case of grade 3 or higher immune effector cell-associated neurotoxicity syndrome. However, this was reported in a patient with concurrent HHV-6 encephalitis.

In order to participate, patients must be at least 18 years of age, a confirmed B-cell malignancy, an ECOG score of 0 or 1, adequate renal, liver, cardiac, and pulmonary organ function, and agree to use acceptable methods of contraception. Patients who received previous CAR T-cell therapy, a history of central nervous system involvement, a seizure disorder, active HIV, a previous or concurrent malignancy, or a primary immunodeficiency disorder are not eligible to participate.

The study is currently recruiting in California, Florida, Georgia, Illinois, Kansas, Massachusetts, Minnesota, Missouri, New York, Oregon, Pennsylvania, Tennessee, Texas, Virginia, and Washington.

See the original post here:
New CAR T-Cell Therapy Appears Safe in B-Cell Malignancies - Targeted Oncology

- Oral and poster presentations to highlight preclinical GeneRide platform data in new indications demonstrating strong evidence of selective advantage of the corrected hepatocytes

Published: Oct. 12, 2021 at 3:05 PM CDT

LEXINGTON, Mass., Oct. 12, 2021 /PRNewswire/ --LogicBio Therapeutics, Inc.(Nasdaq:LOGC), a clinical-stage genetic medicine company pioneering gene editing and gene delivery platforms to address rare and serious diseases from infancy through adulthood, today announced that it was selected to present new data from the company's GeneRide platform in a plenary oral presentation and three poster presentations at the upcoming European Society of Gene and Cell Therapy (ESGCT) Virtual Congress 2021, to be held from October 19-22, 2021.

The oral presentation will include new preclinical GeneRide data showing delivery of corrective genes in three different indications with intrinsic liver damage demonstrating strong evidence of selective advantage of the corrected hepatocytes. Poster presentations will highlight GeneRide expression data in preclinical models of tyrosinemia type 1, as well as the company's optimized adeno-associated virus (AAV) process development.

Oral Presentation Details:

Title: Nuclease-free, promoterless recombinant AAV-mediated genome editing restores function of hepatocytes leading to selective advantage and repopulation in mouse models with liver disease (OR40)Presenter:Shengwen Zhang, Director, Pharmacology, LogicBio TherapeuticsSession: 5b: Gene Editing IIISession date/time:October 21, 2021,17:00-17:15 p.m. CEST (11:00-11:15 a.m. ET)

Poster Presentations Details:

Title: A novel endonuclease-free genome editing technology to edit hepatocytes in vivo led to a full molecular liver transplant and cured mice in preclinical models of Tyrosinemia Type 1 (P253)Q. Qiang Xiong, Director, Head of Preclinical Pharmacology, LogicBio Therapeutics

Title: Development of an Anion Exchange Chromatography Method to Assess Percent Full Capsids for Chimeric Capsid AAV-LK03 (P268)William Lee, Research Associate, LogicBio Therapeutics

Title: Modified plasmid and transfection optimization in suspension HEK293 cells lead to scalable high-yield process for AAV manufacturing (P278)Hans Reuter, Upstream Engineer, Process Development, LogicBio Therapeutics

Additional information on the meeting can be found on the ESGCT website.

The presentation and posters will be available shortly after being presented on the LogicBio Therapeutics website at Presentations | LogicBio Therapeutics, Inc.

AboutLogicBio Therapeutics

LogicBio Therapeuticsis a clinical-stage genetic medicine company pioneering gene editing and gene delivery platforms to address rare and serious diseases from infancy through adulthood. The Company's gene editing platform, GeneRide, is a new approach to precise gene insertion harnessing a cell's natural DNA repair process potentially leading to durable therapeutic protein expression levels. The Company's gene delivery platform, sAAVy, is an adeno-associated virus (AAV) capsid engineering platform designed to optimize gene delivery for treatments in a broad range of indications and tissues. The Company is based inLexington, MA.For more information, visitwww.logicbio.com, which does not form a part of this release.

Investor Contacts: Laurence WattsGilmartin Group(619) 916-7620laurence@gilmartinir.com

Stephen JasperGilmartin Group(858) 525-2047stephen@gilmartinir.com

Media Contacts:Adam DaleyBerry & Company Public RelationsW:212-253-8881C: 614-580-2048adaley@berrypr.com

Jenna UrbanBerry & Company Public RelationsW: 212-253-8881C: 203-218-9180jurban@berrypr.com

View original content:

SOURCE LogicBio Therapeutics, Inc.

The above press release was provided courtesy of PRNewswire. The views, opinions and statements in the press release are not endorsed by Gray Media Group nor do they necessarily state or reflect those of Gray Media Group, Inc.

Read the rest here:
LogicBio Therapeutics to Present New GeneRide Data at the European Society of Gene and Cell Therapy Virtual Congress 2021 - WIBW

Biopharmaceutical companyAchilles Therapeutics has joined the NorthernAlliance for Advanced Therapies Treatment Centre (NA-ATTC) consortium to help expand the centre's cell therapy expertise.

Funded by Innovate UK, the NA-ATTC consortium is a government innovation agency that was created to address the challenges in bringing advanced therapy medicinal products to patients.Specifically, the consortium focuses on all elements of the clinical delivery pathway from procurement of starting materials, through to delivery of clinical trials, and adoption and reimbursement across a range of advanced therapies and indications. Currently, it is one of only threeAdvanced Therapy Treatment Centres in the UK.

"We are delighted to join the Northern Alliance,part of the Advanced Therapy Treatment Centre network,and contribute to this great initiative focusing on multiple aspects of operational delivery," commentedDr Shree Patel, SVP, Clinical Operations at Achilles."We look forward to collaborating and contributing our learnings to the consortium as we work together for the benefit of patients to overcome some of the challenges of cell therapy."

As an industry partner, Achilles will contribute its knowledge and expertise in supply chain and operations for cell therapies that has been developed with its precision clonal neoantigen-reactive T cell therapy (cNeT). Achilles will help the consortium understand the operational gaps in current pathways and practices to be bridged to improve delivery of this type of cell therapy product to patients.

See the original post:
Achilles Therapeutics joins Northern Alliance for Advanced Therapies Treatment Centre - EPM Magazine

This article was originally published here

J Hematol Oncol. 2021 Oct 9;14(1):161. doi: 10.1186/s13045-021-01170-7.

ABSTRACT

BACKGROUND: BCMA-specific chimeric antigen receptor-T cells (CAR-Ts) have exhibited remarkable efficacy in refractory or relapsed multiple myeloma (RRMM); however, primary resistance and relapse exist with single-target immunotherapy. Bispecific CARs are proposed to mitigate these limitations.

METHODS: We constructed a humanized bispecific BM38 CAR targeting BCMA and CD38 and tested the antimyeloma activity of BM38 CAR-Ts in vitro and in vivo. Twenty-three patients with RRMM received infusions of BM38 CAR-Ts in a phase I trial.

RESULTS: BM38 CAR-Ts showed stronger in vitro cytotoxicity to heterogeneous MM cells than did T cells expressing an individual BCMA or CD38 CAR. BM38 CAR-Ts also exhibited potent antimyeloma activity in xenograft mouse models. In the phase I trial, cytokine release syndrome occurred in 20 patients (87%) and was mostly grade 1-2 (65%). Neurotoxicity was not observed. Hematologic toxicities were common, including neutropenia in 96% of the patients, leukopenia in 87%, anemia in 43% and thrombocytopenia in 61%. At a median follow-up of 9.0 months (range 0.5 to 18.5), 20 patients (87%) attained a clinical response and minimal residual disease-negativity ( 10-4 nucleated cells), with 12 (52%) achieving a stringent complete response. Extramedullary plasmacytoma was eliminated completely in 56% and partially in 33% and of 9 patients. The median progression-free survival was 17.2 months. Two relapsed patients maintained BCMA and CD38 expression on MM cells. Notably, BM38 CAR-Ts cells were detectable in 77.8% of evaluable patients at 9 months and 62.2% at 12 months.

CONCLUSION: Bispecific BM38 CAR-Ts were feasible, safe and significantly effective in patient with RRMM.

TRIAL REGISTRATION: Chictr.org.cn ChiCTR1800018143.

PMID:34627333 | DOI:10.1186/s13045-021-01170-7

Continued here:
A bispecific CAR-T cell therapy targeting BCMA and CD38 in relapsed or refractory multiple myeloma - DocWire News

Cell therapy is a type of immunotherapy, or immuno-oncology, where a patients own immune system helps fight and destroy cancer cells. Hoags Cell Therapy Program will conduct a number of cell therapy clinical trials, contributing to the development of promising new therapies for some of cancers most advanced diseases.

Hoag is the first hospital in Orange County to offer cell therapy for solid tumors.

Cell therapy at Hoag studies the use of NK cells, or natural killer cells. These cells are the first responders that help the immune system recognize cancer and initiate a large immune response, resulting in the development of antibodies to fight a patients cancer. These NK cells can stay active in the body much longer than traditional chemotherapy drugs.

NK cells are a type of lymphocyte (a white blood cell) and part of the innate immune system. NK cells play a major role in immunity again viruses and the immunity surveillance of tumors. NK cells express various types of immunoreceptors that are designed to detect changes in cells.

NK cell therapy is the newest immunotherapy, following the introduction of CAR T cell therapy. However, unlike CAR T cell therapy, NK cell therapy has shown to be less toxic, resulting in less side effects. NK cell therapy at Hoag is also used for solid tumors, as opposed to blood cancers, where CAR T cell therapy has typically been applied.

Immunotherapy in the treatment of cancer is here to stay. Cancer experts have seen a number of cell therapy trials that are now meaningfully expanding todays cancer therapeutics, said Burton Eisenberg, M.D., executive medical director, Hoag Family Cancer Institute and the Grace E. Hoag Executive Medical Director Endowed Chair. Hoag is joining the fight and pushing forward on some of the most deadly and challenging cancers to find new trials and therapies to provide new hope to our patients.

For more information on immunotherapy trials at Hoag, please call 866-257-6700 or email clinicalresearch@hoag.org.

Read more from the original source:
Cell Therapy - Hoag

As the cell therapy industry continues to grow, it must face the challenge of creating products that are not only safe and effective, but also affordable. Currently, the prices for approved products ($0.42 million) are too high for most patients, largely because of labor costs, which account for about 50% of the cost of goods in cell therapy manufacturing.

Fully automated cell therapy manufacturing processes could significantly reduce manual intervention and human errors, supporting robust processes, improving product quality, speeding product delivery, and reducing costs. In this article, we will discuss how automated cell therapy manufacturing processes may be achieved with new bioreactor and sensor technologies.

Bioreactors are vessels that permit the careful control of parameters like pH, dissolved oxygen, and temperature to ensure that cells are optimized for cell growth. Bioreactors should culture cells at sufficiently large scales to address the need for cell therapies that can deliver 10810 cells/dose.

In 1944, de Becze and Liebmann created the first bioreactor for compressed yeast production. The first bioreactor designs were large stainless-steel tanks, the bases of which were connected to pipes that could introduce air. Subsequent designs introduced impellers that could facilitate mixing and air bubble dispersal. Eventually, designs were modified to address the requirements of the food and biopharmaceutical industries. For example, designs began to incorporate antiseptic features and real-time monitoring.

Today, various types of bioreactors with special features are commercially available. Bioreactors that are commonly utilized for cell manufacturing include rocking bed, stirred tank, packed bed, and rotating wall vessel bioreactors.

The most commonly used bioreactor for bioprocessing is the stirred tank bioreactor, which is capable of scaling to large volumes (maximum volume: 20,000 L) of cell culture. However, in the stirred tank bioreactor, cell cultures are homogenized using an impeller that turns so vigorously it can affect biological processes. For example, turbulent flows and large shear forces have been found to induce the undesirable, spontaneous differentiation of stem cells.

To minimize the effects of shear forces in bioreactors, researchers developed the rocking bed bioreactor. It uses wave-like motions to ensure low shear stress and to achieve efficient nutrient diffusion. Low shear stress, researchers have found, is crucial for maintaining high cell quality.

Another bioreactor that has similar advantages for culturing sensitive primary cell lines but typically in smaller volumes (<10 L) is the rotating wall vessel bioreactor. As the name suggests, the cells are cultured inside a vessel that is rotated to produce a free-falling state. However, this system requires a complex control system to create precise rotation speeds to induce a free-falling state for continually growing cell populations. For both rocking bed and rotating wall vessel bioreactors, scalability is a challenge.

The aforementioned bioreactors are suitable for culturing non-adherent cells such as immune cells for cancer immunotherapy, but when it comes to adherent stem cells, microcarriers are required. However, the need to completely remove dissolvable microcarriers in the later stages of bioprocessing can lead to technical challenges and regulatory difficulties. To avoid these problems, the packed bed bioreactor has been designed for scalable culture of adherent-dependent cells. For example, this kind of bioreactor has been used to culture muscle cells in synthetic meat applications.

In the packed bed bioreactor, cells are seeded on a fixed bed that consists of a hollow tube with immobilized surfaces such as scaffolds, microcarriers, or porous fibers. Fresh culture media can then continuously circulate within the system to supply oxygen and nutrients. Due to the large surface area, high-density cell culture and cost efficiency can be achieved. Culture media volumes can be smaller, and operations can be less troublesome. However, the high cell densities and difficulty in effectively introducing detachment supplements into the beds can make cell harvesting challenging.

Although the bioreactor types discussed thus far present advantages such as scalability and low shear stress, they all lack the kind of automation that can reduce labor expenses, lower contamination risks, and enhance compliance with Good Manufacturing Practices. Also lacking is automation that could leverage robotics technologies. If robotics could be integrated with modular bioreactors, it would be possible to accelerate and reduce the costs of cell manufacturing.

An example of an automated system is Miltenyi Biotecs CliniMACS Prodigy. It allows users to perform cell activation, transduction, and harvesting in a completely closed and turnkey fashion. Another example is Lonzas Cocoon, a modular cell therapy manufacturing platform. Technologies to automate bioreactors are being pursued not just by individual companies, but by industry consortia such as Autostem, a multidisciplinary mix of engineers, regenerative medicine scientists, and high-technology companies.

One of the greatest needs for cell therapy automation is in autologous manufacturing, says Gregory Russotti, PhD, chief technology officer at Century Therapeutics, a biotechnology company that develops natural killer and T-cell therapies derived from induced pluripotent stem cells. Since every patient requires his or her own batch in an autologous setting, there is no way to scale up processes to produce multiple doses for different patients in larger single batches. Better methods for scale-out are therefore required, in which parallel batches can be processed more efficiently.

One approach would be to automate the processes to reduce labor needs. Automated systems could be configured to process multiple batches at the same time, thereby improving processing efficiencies and driving down the cost of goods.

One of the challenges with designing automated systems for autologous processes is that different cell therapy developers use different processes; therefore, automated methods would need to be customized to each individual process. As the field matures, it is possible that cell therapy developers will converge on some of the process steps, potentially providing the opportunity for standardized automated systems.

Automating these platforms could help reduce the risk of contamination, adds Frank Barry, PhD, professor of cellular therapy at the National University of Ireland, Galway. There are two sources of contamination in the processing of tissue-derived cell productsthe tissue itself and the operators, Barry points out. He adds that most contamination events can be traced to operator actions, such as those involving breaches in the clean room environment. Contamination events due to operators could be reduced through the use of automated robots, which permit hands free procedures and which may be subjected to sterilization.

Automated bioreactor systems are usually designed for small-scale processes, such as the generation of immune cells for personalized cancer immunotherapies. The advantage of such systems is that the cells of individual patients can be manufactured in modular bioreactors. Small, modular, and automated bioreactors can be installed in hospitals rather than remote cell manufacturing factories. This can reduce logistical complexity due to double transportation of cells and minimize cell death due to long cryopreservation periods.

When attempting to enter the clinic, you should not overinvest in technologies or process scales that are not needed for Phase I studies, Russotti advises. Simpler systems at smaller scale will typically enable you to have your process ready for clinical studies more quickly.

However, you should be thinking ahead to what the commercial scale needs to be and have a strategy as to how you will change platforms (that is, bioreactor types) and scale-up your process so that you have a commercially viable process by the time it is needed. Taking this approach inevitably requires process changes which must be carefully planned to minimize the chance of comparability failures.

Sensors are installed in bioreactors to monitor key parameters like pH, temperature, and dissolved oxygen for quality control. One of the most common sensors utilized is the probe-based electrochemical sensor, which can be produced inexpensively and works by detecting changes in electrical potential due to chemical reactions. In general, probe-based sensors can take a wide range of measurements and deliver readings quickly. However, current sensors are typically large and invasive devices. Also, they are fragile and susceptible to electronic interference.

To minimize invasiveness and improve installation flexibility, optical chemosensor systems have been developed that can detect changes in optical properties such as photoluminescence intensity and absorption due to changes in analyte concentration. These systems comprise a light source, indicator dye, optical fiber, and a light detector. Disposable sensor patches can even be placed outside of a bioreactor to minimize the risk of contamination.

Other bioreactor sensors for quality control include spectroscopic sensors. They assess interactions involving molecular bonds and electromagnetic waves to measure key variables such as biomass and abundance of cell debris. Spectroscopic sensors are noninvasive and can measure multiple variables simultaneously with near instantaneous signal delivery. However, the measurements taken with these sensors can be compromised by scattered light. To avoid this problem, the sensors are used in glass reactors.

Unfortunately, most sensor technologies are probe based and incompatible with automated, closed-system, and single-use bioreactors. Moreover, apart from spectroscopic sensors, most sensors are designed to measure a single parameter. The use of multiple invasive sensors necessitates repeated exposure of bioreactor content to the environment, heightening contamination risk.

Multiple parameters can be monitored in real time, however, with capsule technology, which is a combination of autonomous sensor technology and wireless data transmission technology. With capsule technology, wireless sensors, or capsules, are presterilized and precalibrated before they are added to cell cultures, where they float freely. It is also possible to improve the accuracy and resolution of measurements by deploying multiple capsules within the bioreactor.

Automating the monitoring of cell processing will reduce costs, increase efficiency, and improve compliance with Good Manufacturing Practices. According to Mary Murphy, PhD, professor of regenerative medicine at the National University of Ireland, Galway, automated monitoring can allow technicians to control processes remotely. That is, a process occurring inside a facility can be controlled through computer interfaces that are located outside that facility.

Cell culture is one of the most resource-consuming steps of cell manufacturing, and it relies heavily on bioreactors for scalable cell production. Fortunately, bioreactors have come a long way since they were invented for compressed yeast fermentation. They now possess features such as rocking motion technology, which can minimize shear stresses while enhancing cell viability.

However, we can anticipate that the demand for cell-based therapeutic products will increase, and that we will need to automate cell culturing and sensing technologies. Doing so will allow us to rely less on human labor and more on robust processes that will, in turn, allow us to deliver innovative cell-based treatments to patients more quickly, safely, and affordably.

Here is the original post:
Cell Therapy Manufacturing Shifts to Automatic

Research and development of stem cell-based therapies, where a patients own cells, or those from a donor, are used to fight injury and disease, is one of the fastest growing areas in the biotech space. Longeveron Inc. (NASDAQ: LGVN), a clinical-stage biotechnology company in the thick of clinical development, continues to advance its investigational therapeutic, Lomecel-B, for chronic, aging-related and life-threatening conditions.

The company recently announced the results of its randomized, blinded and placebo-controlled Phase 2 trial to evaluate the safety and efficacy of its proprietary Lomecel-B infusion in frail, older patients between 70 and 85 years old. The trial, which was partially funded by the National Institute on Aging, evaluated a single intravenous infusion of 4 different doses of Lomecel-B cell therapy compared to placebo on the change in the distance a person could walk in 6 minutes (a test known as the 6-minute walk test). Results showed that a single infusion of Lomecel-B resulted in an increase in walk distance of approximately 50 meters (164 feet) at 6 and 9 months after infusion, while the placebo-treated subjects showed minimal improvement at 6 months and a deterioration by 9 months.

Lomecel-B is a proprietary allogeneic product comprised of medicinal signaling cells (MSCs) from the bone marrow of adult donors, which are culture-expanded in Longeverons current good manufacturing practice cell-processing facility. According to trial results so far, Lomecel-B, and MSCs in general, may be injected or infused into an unrelated recipient without triggering a harmful reaction (rejection) due to the biochemical properties of these specialized cells. This is in part what makes this class of biologic so intriguing for use as a regenerative therapeutic.

A growing global trend is for biotech companies to direct their services to the cell and gene therapy industry and moving to expand into a new branch of the pharmaceutical contract development and manufacturing organization world.

The U.S. Food and Drug Administration (FDA) has approved a small number of cell and gene therapy drugs. Still, a new product pipeline is fighting for the agencys attention with approximately 1,200 experimental therapies more than half in Phase 2 clinical trials. The annual sales growth estimates for cell therapies are projected to reach 15%.

Longeveron has also initiated a Phase 2 trial evaluating the safety and efficacy of Lomecel-B injection into the heart of children born with hypoplastic left heart syndrome (HLHS), a rare and often fatal congenital heart defect.

Longeveron believes that using the same cells that promote tissue repair, organ maintenance and immune system function can develop safe and effective therapies for some of the most challenging diseases and conditions associated with aging.

We continue to make steady progress advancing our Lomecel-B clinical research programs forward, Longeveron CEO Geoff Green said. We have encouraging top-line results from our Aging Frailty program, and anticipate initiating a Phase 2 trial in Alzheimers disease later this year.

Longeveron shared their review of the Aging Frailty trial data with independent frailty experts, with the objective of planning the next steps for the program. The company presented clinical data at the 2021 International Conference on Frailty & Sarcopenia Research on Sept. 29 during a round-table presentation.

Learn more about Longeveron at http://www.longeveron.com.

2021 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.

See the original post here:
Longeveron Successfully Advancing its Cell-Based Therapy ...