Category Archives: Cell Therapy

This article was originally published here

Curr Med Sci. 2021 Jul 3. doi: 10.1007/s11596-021-2391-5. Online ahead of print.

ABSTRACT

Chimeric antigen receptor T (CAR-T) cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia (ALL), lymphoma and multiple myeloma. However, treatment-related toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have become significant hurdles to CAR-T treatment. Multiple strategies were established to alter the CAR structure on the genomic level to improve efficacy and reduce toxicities. Recently, the innovative gene-editing technology-clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease9 (Cas9) system, which particularly exhibits preponderance in knock-in and knockout at specific sites, is widely utilized to manufacture CAR-T products. The application of CRISPR/Cas9 to CAR-T cell therapy has shown promising clinical results with minimal toxicity. In this review, we summarized the past achievements of CRISPR/Cas9 in CAR-T therapy and focused on the potential CAR-T targets.

PMID:34218353 | DOI:10.1007/s11596-021-2391-5

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Combination of CRISPR/Cas9 System and CAR-T Cell Therapy: A New Era for Refractory and Relapsed Hematological Malignancies - DocWire News

Nova Scotians fighting some types of lymphoma will soon be able to receive a potentially life-saving therapy in their home province.

A new CAR T-cell treatment program is being made possible through $18 million in investments in cancer careannounced Monday by the provincial government.

CAR T-cell therapy is a method of immunotherapy that modifies a person's immune cells or T-cells in a way that the cells are able to detect the cancer and fight it within the patient for the rest of their lives.

About $6.7 million of that funding will be spent annually on the new therapy.

"This will literally be the difference between life and death for patients diagnosed with certain types of cancer," said Dr. Helmut Hollenhorst,the senior medical director of Nova Scotia Health's Cancer Care Program.

Hollenhorstsaid that non-Hodgkin's lymphomas are the fifth most common cancers in Canada and advances in treatment can now cure the illness in about two-thirds of patients.

But the remaining third are only expected to survive for about six monthswhen cancer recurs, he said.

"The CAR T-cell is a type of personalized medicine that has the potential to cure non-Hodgkin's lymphoma when other treatment methods are not available," saidHollenhorst.

The therapy has been approved by Health Canada but specialist staff and equipment are needed, so the proposal for the new program took a couple of years to come to fruition.

About eight patients every year travel from Nova Scotia to Boston for the treatment but others decide not to go due to extra financial costs and added stress to their families.

It's expected now the treatment will be available in Halifax that double that number will take what Hollenhorst describes as a last chance treatment.

"We are committed to providing Nova Scotians with the cancer care and support they need, closer to home," said Health and Wellness Minister Zach Churchill. "These changes add another treatment option not previously available in Nova Scotia and will expand eligibility and ensure patients pay less for travel, accommodations, supplies and cancer drugs."

Churchill said conversations will happen with other Atlantic provinces about the possibility of residents from neighbouring provinces being able to access the treatment.

The Nova Scotia government will also spend $11.1 million in the next three years to reduce out-of-pocket costs for travel, accommodations, supplies and cancer drugs for patients.

About $225,000 of that money will go to the Canadian Cancer Society's Dr. Susan K Roberts Lodge That Gives, which provides free accommodations for people who live outside Halifax while they undergo cancer treatment.

Churchill said the new funds being announced are the result of the 2018 review of cancer services in Yarmouththat included input from patients, physicians, staff and people in the community.

The new CAR T-cell therapy is expected to be available in six months at the QEII Health Sciences Centre.

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N.S. to become first Atlantic province to offer potentially life-saving cancer treatment - CBC.ca

SOUTH SAN FRANCISCO, Calif., June 30, 2021 (GLOBE NEWSWIRE) -- Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) therapies for cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ALLO-605, the Companys next-generation AlloCAR T therapy targeting BCMA for the treatment of relapsed or refractory multiple myeloma. The FDA granted Fast Track designation based on the potential of ALLO-605 to address the unmet need for patients who have failed other standard multiple myeloma therapies. The Phase 1 dose escalation portion of the IGNITE trial evaluating ALLO-605 was initiated in Q2 2021.

ALLO-605 is the Companys first TurboCAR clinical candidate. TurboCAR is a proprietary, next generation platform technology based upon programmable cytokine signaling designed to improve the function and potency of AlloCAR T cells. These properties may also enable CAR T therapy to succeed in solid tumors and increase efficacy in hematologic malignancies. Preclinical results from the ALLO-605 study were presented in a poster session at the American Society of Hematology (ASH) annual meeting in December of 2020.

We are very pleased with the continued momentum of our anti-BCMA portfolio for patients with multiple myeloma and look forward to making allogeneic CAR T therapy a potential option for these patients, said Rafael Amado, M.D., Executive Vice President of Research and Development and Chief Medical Officer. With studies now underway for ALLO-715 alone and in combination with a gamma secretase inhibitor, as well as ALLO-605 as our next generation CAR T, we are taking an aggressive three-pronged approach aimed at exploring the unique attributes of AlloCAR T therapies for patients with rapidly progressing disease.

Initial results from the Phase 1 UNIVERSAL study of ALLO-715 in relapsed/refractory multiple myeloma were presented at an oral session of the ASH annual meeting in December 2020. In April 2021, ALLO-715 was granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA. Separately, the UNIVERSAL study began enrolling patients in the first half of 2021 to evaluate ALLO-715 in combination with SpringWorks Therapeutics investigational gamma secretase inhibitor, nirogacestat.

Fast Track is designed to accelerate the development and review of treatments for serious and life-threatening diseases where no treatment exists or where the treatment in discovery may be better than what is currently available.

About ALLO-605ALLO-605 is a next-generation AlloCAR T investigational therapy that targets the B-cell maturation antigen (BCMA) for the treatment of patients with relapsed/refractory multiple myeloma and other BCMA-positive malignancies. This study uses ALLO-647, Allogene's proprietary monoclonal antibody (mAb), as a part of its differentiated lymphodepletion regimen. ALLO-605 incorporates Allogenes proprietary TurboCAR technology, which allows for cytokine activation signaling to be engineered selectively into CAR T cells. Preclinical results with ALLO-605 were presented at the American Society of Hematology (ASH) annual meeting in December 2020. In June 2021, ALLO-605 was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of relapsed/refractory multiple myeloma.

About Allogene TherapeuticsAllogene Therapeutics, with headquarters inSouth San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T) therapies for cancer. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of off-the-shelf CAR T cell therapy candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visitwww.allogene.com, and follow @AllogeneTx on Twitter and LinkedIn.

Cautionary Note on Forward-Looking StatementsThis press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the ability to progress the Phase 1 IGNITE trial of ALLO-605; the ability of ALLO-605 and other TurboCAR candidates to improve the function and potency of AlloCAR T cells, enable success in solid tumors and increase efficacy in hematologic malignancies; and the potential benefits of AlloCAR T therapy. Various factors may cause differences between Allogenes expectations and actual results as discussed in greater detail in Allogenes filings with the SEC, including without limitation in its Form 10-Q for the quarter ended March 31, 2021. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

AlloCAR T and TurboCAR are trademarks of Allogene Therapeutics, Inc.

ALLO-605 and ALLO-715 utilize TALEN gene-editing technology pioneered and owned by Cellectis. Allogene has an exclusive license to the Cellectis technology for allogeneic products directed at BCMA and holds all global development and commercial rights for this investigational candidate.

Allogene Media/Investor Contact:Christine CassianoChief Communications Officer(714) 552-0326Christine.Cassiano@allogene.com

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Allogene Therapeutics Granted FDA Fast Track Designation for ALLO-605, the First TurboCAR T Cell Therapy, for the Treatment of Relapsed/Refractory...

Each Monday, CancerNetwork highlights the most important content from the previous week in oncology news.

This week, the recap is headlined by an article investigating the differences in genetic risk for breast cancer in Black and non-Hispanic White women. Then, a pair of thought leaders share their thoughts on research presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Black and non-Hispanic White Women Found to Have No Differences in Genetic Risk for Breast Cancer

Differences in frequency of germline pathogenic variants were not seen in patient subsets by ethnicity when comparing 12 genes linked with breast cancer.

At a time when Black men and women are more likely to be diagnosed with cancer at later stages when it is less treatable, [the Black & BRCA initiative] seeks to empower people to understand their family health history and take action to prevent cancer from one generation to the next, said first author Susan Domchek, MD, executive director of the Basser Center for BRCA.

Navigating an Optimal Treatment Course for Advanced Kidney Cancer

Benjamin A. Teply, MD, considers the optimal treatment of renal cell carcinoma in a peer perspective accompanying an article by Tiffany Y. Shaw, MD, and colleagues.

A remarkable sea change has occurred over the past 3-plus years, as the results of 5 separate positive phase 3 studies have demonstrated superiority of immunotherapy-containing regimens over monotherapy with the anti-VEGF tyrosine kinase inhibitor (TKI) sunitinib (Sutent) in the first-line setting.

Neal D. Shore, MD, on the Importance of Multidisciplinary Care in Advanced Prostate Cancer

At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork spoke with Neal D. Shore, MD, FACS, regarding the importance of multidisciplinary care for patients with advanced prostate cancer.

Incorporating a multidisciplinary approach for patients with advanced prostate cancer is essential in order to provide patients with further therapeutic benefit and improve quality of life.

Friendly Competition Fosters Progress in Hematologic Malignancies

With options for transplant, chimeric antigen receptor T-cell therapy, tyrosine kinase inhibitors, and immunotherapy in most tumor types, appropriate therapy selection for a given patient is far from straightforward or standard.

To discuss this and emerging breakthroughs, Elias Jabbour, MD, a professor of medicine in the Department of Leukemia, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston, reflected on his body of work and how competition among colleagues motivated his contributions to the field of medicine.

Stephen Liu, MD, on How Targeted Therapy Results in Significant Efficacy for RET-Altered Tumors

CancerNetwork sat down with Stephen Liu, MD, of the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, to discuss what multidisciplinary providers can learn from outcomes of the phase 2 ARROW trial (NCT03037385) of pralsetinib in patients with RET fusionpositive nonsmall cell lung cancer.

For more updates from CancerNetwork, make sure to follow us on Facebook, Twitter, and LinkedIn to stay up to date on the latest in oncology.

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CancerNetwork's Week in Review: July 5th, 2021 - Cancer Network

T-Cell Therapy Marketis indicating a significant growth rate and likely to be one of the industries that have been contributing to sustaining the international economy.TheT-Cell Therapy market report comprises extensive information in terms of changing market dynamics, latest developments, T-Cell Therapy market and manufacturing trends and structural changes in the market.

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T-Cell Therapy Market Reviewed for 2019 with Industry Outlook to 2027 The Manomet Current - The Manomet Current

American Gene Technologies is celebrating a milestone in its HIV Cure Program, which is currently in Phase 1 human trial. The first participant, an unidentified man.

ROCKVILLE, Md. At a biotechnology company in Rockville, Md., a team of molecular biologists is working to develop cures for cancer, HIV and a range of other diseases.

American Gene Technologies (AGT) is celebrating a milestone in its HIV Cure Program, which is currently in Phase 1 human trial. The first participant, an unidentified man, was treated in late May.

Now, the Food and Drug Administration (FDA) is reviewing the safety of AGTs new cell therapy product, AGT103-T, which is intended to cure HIV.

Were putting viruses in their bodies that are going to specific cells and that are making very, very specific changes in a targeted way, said American Gene Technologies CEO, Jeff Galvin.

The first patient was stellar, Galvin said. Initial safety data is cause to celebrate because what it says is that the process by which we are doing a cell modification for these patients seems to be showing safety.

Galvin is expecting a decision this month, from the Data Safety and Monitoring Board to find out if his team can move forward with treating additional patients.

Most drugs fall out of the development process because of adverse events, so in other words, the drug itself might work on the disease, but the problem may be, people cant tolerate the treatment itself.

With the FDAs approval, Galvin said his team took blood from a man with HIV, to extract his infected T-cells.

HIV is known for hijacking the bodys T-cells, which are cells that fight off some viral infections, thus, weakening the immune system.

Galvins team modified those extracted T-cells from the first participant, to make them resistant to HIV. The reprogrammed cells were infused back into the patient, which, if all goes as planned, would keep the virus from spreading.

We have learned so much about viruses, specifically about HIV, that we can now crack them open, scoop out their disease software, Galvin said. We are so excited at the company and we are trying to contain our excitement because the HIV community has been waiting for a cure for so long.

If AGT gets the green light to move forward with other patients this month, Galvin said, by years end, theyll take blood samples from those participants to see if the modified T-cells are healthy and working as intended. Galvin called it an efficacy signal that will be convincing to the scientific community that the cure for HIV has been achieved or is tremendously close.

This year, we may prove that a functional cure is possible and see the end of HIV in our lifetime, Galvin said.

From that point, and with additional approval from the FDA, researchers would ask some of the participants to stop taking their antiretroviral medication to see what happens to the virus in their bloodstream. After 21 days, Galvin said, theyd have clear indicators revealing the effectiveness of this treatment.

There have been promises of a cure since the first cases of what would later be known as HIV/AIDS.

The Centers for Disease Control and Prevention (CDC) published a report on June 5, 1981, describing a Pneumonia-like disease discovered in five previously healthy gay men in Los Angeles.

Since that study, millions of people have died from HIV/AIDS globally.

What was once a virtual death sentence, is now a manageable disease for some, because of the development of antiretroviral treatments.

In the immediate Washington metropolitan area, 26,824 people are living with HIV, including 39-year-old, Dr. Ravi Perry.

Ive lived far longer than I ever thought I would on the day I was diagnosed, Dr. Perry said. "I genuinely treat every day as a blessing. My immune system still is somewhat compromised. When I get a cold, my colds used to last for a day or two, now it may last four to six days. Your body has a slower response."

Dr. Perry was a junior in college when he was diagnosed on September 4, 2003. While antiretroviral medicines were available at the time, he said, some were too toxic. Dr. Perry was in the hospital consistently because his immune system was weakening and his mental state, waning.

"I certainly remember thinking that I would never be in a relationship, never thought that I would get married, never thought I would have sex again and thought that my life was on its way to its expiration date, Dr. Perry recalled.

For the last 15 years, Dr. Perry said, hes been undetectable.

Ive been able to live a mostly normal life, even with HIV. Its not something I expected to get, but I was 21 when I was diagnosed. Ive grown accustomed to telling that story because I think its important for younger people, Perry said.

As Chair of the Political Science Department at Howard University, Dr. Perry reminds students on campus about the seriousness of this virus. He also tells his story at local churches and community events.

My hope is that people realize the seriousness of HIV, but that people are living with HIV and not dying as much from AIDS anymore. The stigma associated with it, I think, certainly has no place in society, Dr. Perry added.

While Dr. Perry doesnt expect a cure to be developed in his lifetime, he said there are steps to take to eliminate HIV. First, with equal emphasis on prevention and intervention.

We seem to be focused on prevention because of course, most of the world is negative, Dr. Perry said. We all can be doing more to help ensure this disease doesnt ravage another generation. We can be donating our time to HIV/AIDS organizations. We can be lobbying the Red Cross to lift their ban on gay men not being allowed to give blood. We can be lobbying our congress members to eliminate these HIV criminalization laws that are abhorrent and from another era. We can of course in our own personal and private lives be ensuring we are having conversations with our nieces, our nephews, our cousins about HIV and sexual health."

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'We're in it to win it' | Maryland company progresses with development of HIV 'functional cure' - WUSA9.com

As Legend Biotech andJohnson & Johnson's multiple myeloma cell therapy prospect nears the FDA finish line, the companies are moving to carve out a manufacturing foothold in Europe.

Through a joint investment with J&Js Janssen unit, Legend has drawn up plans for a new cell therapy facility in Belgium, which the partners will use to boost global production capacity for their multiple myeloma drugcilta-cel, plus other cell therapies, Legend said in a release.

The move comes just a few months after Legend and J&J completed their rolling FDA submission for the CAR-T therapy, which is up for a decision on November 29 after scoring a priority review tag in May.

If cleared, cilta-cel would be forced to play catch up with Bristol Myers Squibb and bluebird biosmultiple myeloma cell therapy ide-cel, now dubbed Abecma, which became the first CAR-T approved for the disease in late March.

RELATED:10 biotechs to know in China-Legend Biotech

The new Belgian plant, expected to come online by 2023, marks Legends first manufacturing foray into Europe. The company also operates a pair of clinical and commercial-scale factories in New Jersey, plus a plant in China. It alsoboasts R&D operations in China, Ireland and the United States, its website says.

Legend didnt name the size of its investment and offered little in the way offactory specs. The company didnt immediately respond to Fierce Pharmas request for comment.

For its part, Janssen is headquartered in Beerse, Belgium, and runs R&D, manufacturing, distribution and clinical pharmacology sites in the country, where it says it employs more than 5,000. By setting up shop there, Legend hopes to tap into the areas vast talent pool and make use of the countrys strong life sciences ecosystem, Liz Gosen, senior vice president of global technical operations at Legend, said in a statement.

Despite trailing BMS and bluebird to the market, cilta-cel is poised to put up a fight, analysts noted earlier this year. We think around 8-9 months difference in the timing of market arrival does not offer much first mover advantage for [BMS/bluebird bios] ide-cel given its inferior clinical profile to cilta-cel, analysts at Jefferies wrote to clients in April.

RELATED:Bristol Myers Squibb, bluebird bio finally take their multiple myeloma CAR-T across the FDA finish line

At theannual meeting of the American Society of Hematology in December, investigators presented data showing that Legend and J&J's CAR-T drug banishedmultiple myeloma in two-thirds of patients and shrank tumors in 97%. And in a data update at the American Society of Clinical Oncology earlier this year,cilta-cel postedan overall response rate of 98% and yielded a stringent complete response in 80% of patients after a median follow-up period of 18 months. The drug achieved an 18-month progression-free survival rate of 66%.

Legend, which spun out of Genscript Biotech, made a splash last year with a massive $424 million initial public offering, landing the no. 2 spot on Fierce Biotechs list of 2020s top biotech IPOs.

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J&J cell therapy partner Legend carves out production foothold in Belgium as myeloma drug nears finish line - FiercePharma

CARLSBAD, Calif.--(BUSINESS WIRE)-- Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, today provided an update on the clinical advancement of OPC1, its investigational allogeneic oligodendrocyte progenitor cell (OPC) transplant therapy for the treatment of spinal cord injury (SCI). Following feedback received from an interaction held with the U.S. Food and Drug Administration (FDA) last week under the FDAs Regenerative Medicine Advanced Therapy (RMAT) program, Lineage intends to submit an amendment to its Investigational New Drug application (IND) for OPC1 to support a Phase 1 clinical study to evaluate the safety and performance of Neurgain Technologies Inc.s Parenchymal Spinal Delivery System (Neurgain PSD system) to deliver OPC1 cells to the spinal cord. In February, the Company entered into an exclusive option and license agreement with Neurgain to evaluate its novel PSD system in both preclinical and clinical settings. The IND amendment is expected to be submitted to the FDA in the fourth quarter of 2021. The data from the Phase 1 clinical study is intended to validate the Neurgain PSD system for use in a late-stage clinical study, expected to begin in 2022 following the completion of the Phase 1 study.

It is a privilege to report that our novel OPC1 program will be returning to clinical testing earlier than anticipated. There currently are few opportunities for SCI patients to participate in clinical trials, so we are excited to re-engage with these patients and their advocacy community as part of our efforts to improve outcomes for individuals with this debilitating condition, for which there are no FDA-approved treatments, stated Brian M. Culley, Lineages CEO. In the past 18 months, we have significantly increased the purity and production scale of the OPC1 cells utilized in a prior clinical study. This improved production process has been transferred to our in-house Current Good Manufacturing Practice (cGMP) suite and will support production of clinical study material for later-stage clinical work. In parallel, we are finalizing plans to test the safety of the Neurgain PSD system to deliver OPC1 in SCI patients. We believe this device can improve the ease and precision of delivering our cells to the spinal parenchyma. As an added benefit, based on feedback from the FDA, in addition to patients with subacute SCI, we anticipate that patients with chronic SCI also will be eligible for enrollment in this study. Gaining additional OPC1 safety and device performance data across a broader range of patients and injury types will be more informative to the program and support further product and device development. Our recent accomplishments in areas of production and delivery contributed real-world feasibility to the promising clinical results previously reported with this program, in which OPC1 demonstrated improvements to quality of life and motor function for certain SCI patients. Importantly, we are working to be in a position to initiate a late-stage clinical study in SCI next year.

The Neurgain PSD system has been designed to allow for the administration of cells to the spinal cord without stopping the patients ventilator during the procedure. Elimination of the need to stop respiration during surgery is expected to reduce the complexity, risk, and variability of administering cells to the area of injury. The Neurgain PSD system has been designed to provide delivery of cells with accurate anatomical positioning and dosing, is more compact than existing devices and is attached directly to the patient during the procedure. This innovative delivery system is expected to provide a significant improvement in usability and provide more flexibility to the surgeon when compared to the methods and tools utilized to deliver OPC1 cells in the completed Phase 1/2a SCiStar study of OPC1 for the treatment of cervical SCI. Neurgain Technologies, Inc. is a medical device company that is developing technologies developed by neurosurgeons at the University of California San Diego.

Lineage plans to evaluate the safety and performance of the Neurgain PSD system to deliver OPC1 to the spinal cord in both the preclinical and clinical setting. If results of these studies are positive, Lineage may exercise its option to enter into a pre-negotiated license and commercialization agreement with Neurgain. Pursuant to that agreement, Lineage may integrate the Neurgain PSD system into a late-stage clinical trial and, if approved, commercial use of OPC1 for the treatment of patients with spinal cord injury. There currently are no FDA approved treatments for spinal cord injury.

About Spinal Cord Injuries A spinal cord injury occurs when the spinal cord is subjected to a severe crush or contusion and frequently results in severe functional impairment, including limb paralysis, aberrant pain signaling, and loss of bladder control and other body functions. There are approximately 18,000 new spinal cord injuries annually in the U.S. The cost of a lifetime of care for a severe spinal cord injury can be as high as $5 million.

About OPC1 OPC1 is an oligodendrocyte progenitor cell (OPC) transplant therapy designed to provide clinically meaningful improvements in motor recovery in individuals with subacute spinal cord injuries. OPCs are naturally occurring precursors to the cells which provide electrical insulation for nerve axons in the form of a myelin sheath. While variability exists for the precise duration of each phase, subacute SCI generally refers to the phase that is three to six weeks post-injury and chronic SCI refers to the phase beginning after the subacute phase. The OPC1 program has been partially funded by a $14.3 million grant from the California Institute for Regenerative Medicine (CIRM). OPC1 has received Regenerative Medicine Advanced Therapy (RMAT) designation for its use in subacute cervical SCI and Orphan Drug designation from the FDA.

About Lineage Cell Therapeutics, Inc. Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineages programs are based on its robust proprietary cell-based therapy platform and associated in-house development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed to either replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineages clinical programs are in markets with billion dollar opportunities and include three allogeneic (off-the-shelf) product candidates: (i) OpRegen, a retinal pigment epithelium transplant therapy in Phase 1/2a development for the treatment of dry age-related macular degeneration, a leading cause of blindness in the developed world; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase 1/2a development for the treatment of subacute spinal cord injuries; and (iii) VAC2, an allogeneic dendritic cell therapy produced from Lineages VAC technology platform for immuno-oncology and infectious disease, currently in Phase 1 clinical development for the treatment of non-small cell lung cancer. For more information, please visit http://www.lineagecell.com or follow the Company on Twitter @LineageCell.

Forward-Looking Statements Lineage cautions you that all statements, other than statements of historical facts, contained in this press release, are forward-looking statements. Forward-looking statements, in some cases, can be identified by terms such as believe, may, will, estimate, continue, anticipate, design, intend, expect, could, can, plan, potential, predict, seek, should, would, contemplate, project, target, tend to, or the negative version of these words and similar expressions. Such statements include, but are not limited to, statements relating to advancement of the clinical development of OPC1 to treat SCI, OPC1s potential to improve quality of life and/or motor function for patients with SCI, the potential benefits of using the Neurgain PSD system to deliver OPC1 for the treatment of SCI, OPC1s regulatory approval pathway, and Lineages potential exclusive license and commercialization agreement with Neurgain. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Lineages actual results, performance or achievements to be materially different from future results, performance or achievements expressed or implied by the forward-looking statements in this press release, including risks and uncertainties inherent in Lineages business and other risks in Lineages filings with the Securities and Exchange Commission (SEC). Lineages forward-looking statements are based upon its current expectations and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. Further information regarding these and other risks is included under the heading Risk Factors in Lineages periodic reports with the SEC, including Lineages most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the SEC and its other reports, which are available from the SECs website. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Lineage undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

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Lineage's OPC1 Cell Therapy for the Treatment of Spinal Cord Injury to Return to Clinical Testing - BioSpace

Corning HYPERStack 36-layer and 12-layer cell culture vessels

Mesenchymal stem cells (MSCs) are used frequently for cell therapy applications. As multipotent cells, they can differentiate into other lineages such as adipocytes, osteocytes, and chondrocytes. Additionally, they are known to secrete trophic factors that can play important roles in immunoregulation. Although MSCs can be isolated from several different tissue sources, those derived from bone marrow commonly are studied because they are easy to access in quantities large enough for therapeutic dosing (2 106 cells/kg of body weight). Still, that equates to 140 million cells for a 150-pound individual. And the process of expanding MSCs to achieve such quantities can introduce risks for heterogeneity-induced quality failures. Chances of clinical success can improve with a manufacturing process that maintains a homogeneous MSC population after expansion to meet required critical quality attributes (CQAs).

Once cells are scaled up, they need to be cryopreserved for stability and transport. Cryoprotectants such as dimethyl sulfoxide (DMSO) often are added to freezing media to reduce ice formation and increase cell survival after thawing. However, because DMSO can be cytotoxic, its final concentration in a drug product must be minimized. Tools from Corning Life Sciences can help scientists and drug developers meet growing demand for bone-marrowderived MSC therapies.

Figure 1:Expansion of human mesenchymal stem cells (MSCs) in a Corning HYPERStack-36 vessel; MSC densities ranging from 4.4 104 to 5.2 104 cells/cm2 were achieved after five days of culture. Across three studies, total MSC yield averaged 8.7 108 cells per HYPERStack-36 vessel, with >90% average MSC viability.

Mesenchymal Cell Scale-UpMSCs are adherent cells that are sensitive to manufacturing process changes. That sensitivity can complicate scale-up to large quantities. When cultured under suboptimal conditions, MSCs can lose their multipotency. Corning HYPERStack 36-layer cell culture vessels offer a solution. A HYPERStack unit uses proprietary technology to provide a large surface area in a compact footprint. That technology relies on an ultrathin, gas-permeable film to facilitate gas exchange in each layer of the vessel. Each HYPERStack module comprises 12 individual chambers featuring Corning CellBIND surface treatment for optimal cell attachment. One module provides 6,000 cm2 of surface area; three modules can connect to form a HYPERStack 36-layer vessel, totaling 18,000 cm2 of growth surface area.

When human bone-marrowderived MSCs are cultured in a HYPERStack 36-layer vessel, yields of >800 million viable cells can be achieved (Figure 1). Harvested cells show high viability and expression of markers demonstrating MSC multipotency (Figure 2). Such results show that large-scale expansion of MSCs in a HYPERStack vessel generates a homogeneous population of cells that maintain necessary CQAs.

Figure 2: Mesenchymal stem cells (MSCs) recovered from a Corning HYPERStack 36-layer cell culture vessels show >99% expression of CD90, CD105, and CD73 markers while expressing <0.5% of differentiation markers (CD45, CD34, CD11b, CD19, and HLA-DR).

Corning cryopreservation bags remain flexible at ultralow temperatures(e.g., 196 C).

Large-Scale CryopreservationCryopreservation of large quantities of cells has become an important strategy for simplifying cell therapy workflows because it increases product shelf life, allows time for quality testing, and lengthens the period of potential administration. Cryopreservation bags are designed for single-use storage, preservation, and transfer of large volumes of cells. Cornings cryopreservation bags are novel bag-film containers that can remain flexible at ultralow temperatures (196 C) because they are made from a proprietary polyolefinethyl vinyl acetate blend. Corning produces the bags in four sizes covering fill volumes between 20 mL and 190 mL, with demonstrated performance for storage of bone-marrowderived MSCs.

The Corning X-WASH system performs DMSO removal in a closed, sterile format.

DMSO RemovalDMSO can serve as a cryoprotectant for a wide range of cell types. It often accounts for 510% of a freezing solution to reduce ice formation and maintain cell viability. But because of its cytotoxic effects, DMSO must be removed as much as possible from a final cell therapy product. That can be accomplished by centrifugation and buffer exchange.

The Corning X-WASH system can perform those steps in sterile, closed conditions (Figure 3). The X-WASH system also uses highly sensitive infrared sensors and software to transfer process data from the X-WASH control module to a database. That feature supports good manufacturing practice (GMP) data processing, monitoring, and reporting. Ultimately, the X-WASH system is designed to wash, resuspend, and condense cell suspensions without compromising product quality.

Corning has used the X-WASH system to reduce the DMSO concentration from a bone-marrowderived MSC product. About 70 million human MSCs were processed into Corning cryopreservation bags containing 10 mL of a 90% fetal bovine serum (FBS) and 10% DMSO solution. MSCs were thawed into 200 mL of phosphate-buffered saline containing 2% human serum albumin and 5% glucose. Cells were added to X-WASH cartridges for processing, then analyzed for recovery (Figure 4), viability (Figure 5), and multipotency (Figure 6). Ultraperformance liquid chromatography (UPLC) was used to quantify DMSO reduction. UPLC analysis showed that 200-mL dilution followed by a 200-mL wash in an X-WASH system reduced the final DMSO concentration by at least40 fold.

Figure 3:Corning X-WASH system workflow to remove dimethyl sulfoxide (DMSO)

Figure 4:Recovery of human mesenchymal stem cells (MSCs) after washing with a Corning X-WASH system; the bars below represent MSC density, and cell viability levels are represented as dots.

Considerations for Closed Systems and Custom MediaClosed-system cell-culture products help reduce contamination risks during drug development and manufacturing. Thus, they should be considered when planning for cell-culture operations. Ordering multiple components and assembling tubing sets in house can add complexity and time to cell therapy processes. To aid in the development of such processes, Corning offers preassembled closed systems and aseptic-transfer caps that are compatible with many Corning cell culture vessels.

Figure 5:Human MSC multipotency as represented by average marker expression after processing with a Corning X-WASH system (with standard deviation, n = 3)

Corning closed-system solutions arrive at your facility sterile and ready to use. They mitigate contamination risks, reduce the time and expense of sourcing and assembly, and improve overall productivity. Moreover, Cornings extensive library of fully validated filters, connectors, tubing, and clamps enables customized design of a closed-system solution for a specific application.

In cell-based therapies, cultured cells are the final product, requiring different manufacturing processes from those used for conventional biologics production. Major considerations in cell therapy scale-up include culture vessels and media as well as cells themselves. Inadequate attention to culture equipment and raw materials not only can diminish a therapys efficacy, but also can result in regulatory challenges that might delay a candidates progress through development. Because culture media are linked to cell growth and productivity, they rank among the most critical aspects of process development during scale-up.

Figure 6:Dimethyl sulfoxide (DMSO) concentration in final product after 200-mL dilution followed by 200-mL wash in a Corning X-WASH system (data from three independent runs)

Although off-the-shelf media can provide fast and efficient solutions during early stages, they can have trouble meeting specific scale-up conditions later on. Moving from small-scale, small-volume, static cultures into large-scale, large-volume vessels can trigger a host of additional requirements that cannot be addressed easily using an off-the-shelf solution. Customization by a media manufacturer is an attractive solution to concerns associated with large production scales, including media stability, packaging, handling, and storage. Custom media solutions also help to derisk processing. Cornings high-quality custom development and manufacturing services can produce tailored media and reagents to meet cell therapy production needs.

Simplifying Cell Therapy WorkflowsAddressing the growing demand for cell-based therapies requires optimization of scale-up, cryopreservation, and DMSO removal. With some human MSC therapies requiring as many as one billion cells per dose, cell therapy companies need efficient ways to scale up production of homogeneous MSCs that meet CQAs. Additionally, large quantities of MSCs will need to be cryopreserved to simplify cell therapy workflows. Before product administration, DMSO and other reagents used during the manufacturing process will need to be reduced. Corning offers solutions to simplify the complete range of cell therapy workflows.

Hilary Sherman is senior scientist, and Chris Suarez is field applications manager at Corning Life Sciences, 836 North Street, Tewksbury, MA 01876; ScientificSupport@Corning.com; 1-800-492-1110.

CellBIND, HYPERStack, and X-WASH all are registered trademarks of Corning Incorporated.

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Cell Therapy Workflows Using Corning HYPERStack: MSC Production - BioProcess Insider

A biotech spin-out from Cancer Research UK has been given FDA approval to trial its T-cell therapy in humans.

GammaDelta Therapeutics will test its T-cell therapy in a clinical trial expected to begin later this year. The trial will assess the safety of GammaDeltas treatment and look for early indications of efficacy in people with a type of blood cancer called acute myeloid leukaemia (AML).

GammaDelta currently has four treatments in its pipeline, two of which are focused on treating haematological malignancies such as blood cancer. The company is looking at the clinical applications of allogeneic therapies based on gamma delta T lymphocytes. Gamma delta T cells make up only a small number of all the T cells in the body. Whilst they are less abundant, GammaDelta says they have distinct properties that give them promise as a potential cancer therapy.

Unlike the more abundant alpha beta T cells, which rely on a specific molecule to help them recognise red flags on cells, gamma delta T cells scan the surface of cells directly to spot potential threats. Because of this, GammaDeltas T cell therapy could help treat patients whose cancer cells have tried to evade the immune system by removing certain molecules from their surface, making them invisible to alpha beta T cells.

From our very first studies into T cells in the 1980s, through to demonstrating their unique activity in the presence of cancer, its been clear that these immune cells have enormous potential for the development of new immunotherapy treatments, said Adrian Hayday, scientific founder of GammaDelta.

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Cancer Research UK spin-out to trial T-cell therapy for blood cancer - EPM Magazine