An emerging industry looks to take T cells to the cryobank
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An increasing body of evidence shows that using younger, less heavily pretreated T cells results in more effective chimeric antigen receptor T-cell therapies.
Research in this area has gained the attention of Silicon Valley investors who are looking to capitalize on a potential business opportunity: commercial cryobanking of T cells for future use in cell-based therapies.
Is this type of savings plan based on sound evidence, or is it a potential money grab that capitalizes on concerns about future health? HemOnc Today investigated whether there is a clinically relevant benefit to cryobanking T cells at an early age for treatment later in life.
Current research
Cryobanking cells for future use has precedent. Cord blood banking, in which stem cell-rich blood is extracted from the umbilical cord after birth, with the stem cells preserved for future use in research or transplant procedures, has emerged as a growing industry.
The market for cord blood banking is projected to surpass $8 billion annually by 2025, up from approximately $3 billion in 2016, according to analysts at Transparency Market Research. About two-thirds of this growth will come from private blood banks that allow individuals to have their baby’s umbilical cord blood cryopreserved for potential use in future stem cell transplants to treat diseases such as leukemia or lymphoma.
Research has shown that T cells taken from patients with malignancies before they experience relapsed or refractory disease, and thus are exposed to multiple lines of therapy, may make for more effective treatments.
“CAR T cells manufactured from leukapheresis samples obtained after response to induction therapy would be, on average, more clinically effective than those obtained from heavily relapsed/refractory [patients with] multiple myeloma,” Alfred L. Garfall, MD, assistant professor of medicine in the division of hematology oncology at University of Pennsylvania’s Perelman Center for Advanced Medicine, and colleagues wrote in a study published in Blood Advances.
T-cell expansion in vivo appeared to be dependent on disease type and exposure to previous therapy among children with B-cell malignancies, according to results of a study published in Science Translational Medicine. The investigators also found that early lineage T cells were associated with better expansion.
“Enrichment of early lineage subsets is associated with significantly improved in vitro expansion,” Nathan Singh, MD, assistant professor in the department of medicine at Washington University School of Medicine in St. Louis, and colleagues wrote.
“Patients with [acute lymphoblastic leukemia] have T cells with enhanced expansion capability as compared to patients with [non-Hodgkin lymphoma],” they added. “The poor expansions from our [non-Hodgkin lymphoma] samples are strongly associated with an initial and maintained deficit of early lineage cells, highlighting a fundamental difference in the T-cell compartments at the time of diagnosis, implicating a disease-driven depletion of early lineage cells in lymphoma that is not present in leukemia.”
A different kind of bank
Entrepreneur Kevin Kirk aims to open what his fledgling company calls “the world’s first T-cell bank.” So far, he’s armed with an idea and more than $1 million in initial funding from Silicon Valley investors.
Kirk is founder and CEO of Cell Vault, a startup that has partnered with some health care industry giants to collect and cryogenically store healthy T cells for future use in cellular therapies. The premise of the operation is that younger cells are stronger and will be more potent when they are needed to manufacture something such as a CAR T-cell therapy.
“You are paying for peace of mind, and that’s basically what we are offering,” Kirk told HemOnc Today.
A kit is shipped to the customer and a phlebotomist from Quest Diagnostics, one of the company’s partners, arranges an in-home or in-office 50 mL blood draw. Kirk said this amount has been recommended by experts to “make sure we have banked enough cells that will contain enough viable T cells.”
The kit is then shipped to the laboratory at Brooks Life Sciences in New Jersey, where the samples are processed and stored for future use.
The total cost of the service starts at $300 per year, plus the fee for the blood draw. Discounts for prepaid multiyear plans are available that waive the blood draw fee and lower the price to around $100 per year. Kirk said a monthly option for customers also is being considered.
The service will only store cells from healthy individuals, so those recently diagnosed with a particular disease approved for cellular therapy could not cryobank their cells for future use. Additionally, Cell Vault’s services are available only to customers aged 13 years and older.
When asked whether the service is based on sound science coupled with unmet need and not just a money grab, Kirk acknowledged that the idea has been “getting the flak and criticism that comes with being first to market.”
“Our intentions are in the right place, and we are excited to take this service to market,” he said. “Our goal is to get to a point where the scale cost can get low enough that this is something a primary care doctor can offer. I think most people would do this just to know that they have the youngest, strongest version of themselves set aside in case it needs to be used in the future.”
‘Perfect predictor’ lacking
Improving the effectiveness of cellular therapies has been a longtime goal of David Barrett, MD, PhD, assistant professor of pediatrics at the University of Pennsylvania’s Perelman School of Medicine and pediatric oncologist in the cancer center at Children’s Hospital of Philadelphia.
Barrett, an expert in the field of CAR T-cell therapy, and his lab have focused specifically on which T cells result in more robust cellular expansion.
Barrett said that after the first successful treatment with CAR T cells at Children’s Hospital of Philadelphia in 2012, dozens of patients were referred to the hospital to see if heavily pretreated children with advanced disease could benefit from the therapy. They found that previous regimens of toxic chemotherapy had depleted many of the children of T cells, leaving none to collect.
“Early on we asked the question: Is there a right time to collect T cells from children with cancer?” Barrett said. His lab’s research suggests that prior to therapy exposure will be one answer to this question.
Barrett recently co-authored a study, published in Cancer Discovery, that examined the impact of chemotherapy on T cell types and subsequent manufacturing of cell therapies for children with hematologic malignancies.
“The conclusion we came to is that most children, especially those with leukemia, have great T cells in the beginning but that we progressively reduce their potential with more and more intensive chemotherapy,” he told HemOnc Today. “The earlier you collect T cells from a child undergoing chemotherapy, the more likely they will be suitable for use for the purpose of manufacturing a CAR T-cell product.”
The implication, Barrett noted, is that all children have perfectly usable T cells unless they get cancer and are exposed to treatment; therefore, collecting and cryobanking T cells at an early age for later use would be beneficial, theoretically. However, many challenges exist, and evidence to support this assumption remains incomplete.
Barrett said that there are no 100% sensitive biomarkers to ensure T cells being collected will be useful in future cellular therapy manufacturing. The study in Cancer Discovery revealed some good biomarkers, such as higher levels of naive T cells, but this is only half predictive, he said. The same is true for older memory or effector T cells, which, when manufactured into a CAR T product, are likely to be less effective.
“That’s the theory anyway, and that’s what the data support. But it’s not a perfect predictor,” Barrett said. “It does not tell us for sure for every patient if those T cells will be suitable for CAR T-cell production.”
Barrett said there is absolutely a benefit to cryobanking T cells for children who have already been diagnosed with lymphoma or leukemia and whose parents are concerned about being able to use an approved cell therapy product in the future. He said his institution has recommended this approach for high-risk patients, but the challenge is the fees associated with storage if a patient is not enrolled in a clinical trial.
For healthy children, Barrett said that cryobanking T cells potentially is a good idea, but anyone who invests in a commercial service should be aware of the limitations.
“If you are going to bank cells, you need to know what you are banking and that banking is going to be compliant with and eligible to be used in cell therapy trials,” he said.
One potential pitfall Barrett highlighted is whether enough cells from a 30-pound child aged 5 years would be banked to treat a 150-pound adolescent aged 16 years.
“There are real practical issues to banking for future use in healthy children that I don’t think anyone has sorted out yet,” Barrett said.
Regardless, Barrett believes the idea of cryobanking T cells for future use could be clinically useful.
“One of the challenges is that even for people in cell therapy trials, there are strict criteria for when and how you do T-cell collection,” he said. “It makes sense to collect healthy T cells from healthy children and bank them if that’s something you want to do, but we completely lack the understanding of what the collection should look like, and that is the big challenge.” – by Drew Amorosi
References:
Das RK, et al. Cancer Discov. 2019;doi:10.1158/2159-8290.CD-18-1314.
Garfall AL, et al. Blood Adv. 2019;doi:10.1182/bloodadvances.2019000600.
Singh N, et al. Sci Transl Med. 2016;doi:10.1126/scitranslmed.aad5222.
Transparency Market Research. Umbilical cord blood banking market to expand at a strong 11.4% CAGR, vast applications in cell-based therapies to boost rapid expansion. Available at: www.prnewswire.com/news-releases/umbilical-cord-blood-banking-market-to-expand-at-a-strong-11-4-cagr-vast-applications-in-cell-based-therapies-to-boost-rapid-expansion---tmr-300907388.html. Accessed Nov. 25, 2019.
For more information:
David M. Barrett, MD, PhD, can be reached at Children’s Hospital of Philadelphia, 3501 Civic Center Blvd., CTRB 3016, Philadelphia, PA 19104; email: barrettd@email.chop.edu.
Kevin Kirk can be reached at 2727 N. Atlantic Ave., #703, Daytona Beach, FL 32118; email: kevin@cellvault.com.
Disclosures: Kirk is founder and CEO of Cell Vault, a provider of T-cell cryobanking services. Barrett reports no relevant financial disclosures.