The landscape of stem cell therapy is rapidly evolving and delivering new means of regenerative treatments that, at one time, were considered improbable. The ability to successfully treat certain diseases with stem cells obtained from umbilical cord blood, bone marrow, and adipose tissue is groundbreaking; there have been over 40,000 umbilical cord blood transplants alone.
As the world’s first cord blood bank, Cryo-Cell International is committed to advancing the scope of utilizing stem cells in regenerative medicine. We are passionate about this mission, and while doing so, we ensure that we adhere to the highest industry standards by being one of the only private cord blood banks also to be FACT accredited. With each family we help, and with each transplant that is performed worldwide, employing the power of stem cells, we are in the metaphorical stands cheering and applauding.
Along these metaphorical terms, we are profoundly disheartened when a few bad teams attempt to undermine the integrity of the sport. As the old adage goes, “A few bad apples can spoil the whole bunch.” In this case, we take aim at some of the third-party companies that attempt to offer promise on products that are not based on sound scientific evidence, or good manufacturing practices.
Recently, there has been a proliferation of start-up companies to cryogenically preserve the blood of adults for future use. The hope in doing so is that clients may be able to use the T-cells present within their blood to fight certain cancers, should cancerous cells manifest later in life. These companies have come under recent scrutiny after the International Society of Cell & Gene Therapy (ISCT) issued a consumer alert. What did the ISCT determine? In a nutshell, storing adult stem cells for future use is unwise. We support the ruling of the Food and Drug Administration (FDA) and ISCT’s stance. Let’s address the what, how, and why.
What Are T- Cells and What is T-Cell Therapy?
T-cells are white blood cells that play a crucial role in the body’s immune system. These cells act as responders that seek out and destroy targeted foreign cells. MD Anderson Cancer Center explains the process of Chimeric Antigen Receptor (CAR)-T therapy which is a type of immunotherapy that has shown success in patients with certain cancers such as large B-cell non-Hodgkin’s lymphoma and B-cell acute lymphoblastic leukemia (ALL). Their website outlines that process starting with apheresis, a special kind of blood draw where certain elements of the blood are extracted, and the remaining blood is channeled back into the patient. The T cells from the blood are sent to a lab where they are then genetically modified to produce a protein, known as a receptor, that is able to identify another protein (called an antigen) located on the surface of cancer cells. These “beefed” up T cells are able to distinguish and attack the cancer cells.
To date, there are only two types of FDA approved CAR T-cell therapies: Kymirah, typically used for pediatric and young adult patients with ALL; and Yescarta, used for patients with B-cell non-Hodgkin’s lymphoma. Note that both treatments are only used as a last resort measure when a patient has been treated unsuccessfully with at least two other cancer treatments or has relapsed from prior treatment attempts.
Why Are There Objections to Third-Party T Cell Blood Banks?
According to a statement released from ISCT last month, Bruce Levine, Ph.D and President-Elect of ISCT announced, “Currently, companies are promising an undeliverable service. The commercial use of CAR-T cells employs the collection procedure of apheresis to remove billions of white blood cells for further processing. If and when a commercial product is developed in the future that could utilize as few cells as could be obtained from a small blood draw, there would be extensive quality and regulatory requirements for CAR-T therapy providers to use pre-stored T-cells from a third-party banking service. Marketing this service today as a prelude to a potential therapy in the future to cancer patients, and especially to healthy people, is misleading.”
Unlikely and Costly
Considering that CAR-T cell therapy is only used in response to other failed treatments, and also that it has only been approved for a very small subgroup of blood cancers, the likelihood of patients to be eligible for CAR-T cell therapy is slim to none. According to one source, the odds of a healthy person being eligible for CAR-T therapy is less than 1 in 100,000 per year. Also, the only two approved FDA treatments of this nature are costly, with Kymirah costing around $475,000 and Yescarta priced around $373,000. Some of the T-cell banks offer their services at varying price points for annual storage plans with collection fees as much as $700 or more.
This is a hefty price tag to pay for a service that is not guaranteed to work, or even be accessible to a client. The disclaimer on one such company’s website reads, “The use of cryopreserved cells for such therapy is currently not approved by the FDA. Much is unknown about the usability of one's own T-cells that have been cryopreserved. For example, it is unknown whether T-cells collected and cryopreserved will be able to be used for cellular therapies, including CAR-T cell production. There is no guarantee that your cryopreserved cells will have a future therapeutic use…” Indeed, there are too many unknown variables; including the safety and feasibility of such therapies. In a recent article, one start-up founder admits that, “CAR-T has only ever been done with T cells from people who have had cancer—it's never been done with healthy cells before…No one has collected them ahead of time, before someone's health has become compromised.”
Side Effects and Clinical Trials
There are severe and sometimes deadly side effects that can occur during CAR T-cell therapy. Among these are cytokine release syndrome, which leads to high fever, abnormally low blood pressure, difficulty breathing, and organ failure. According to the European Hematology Association, the frequency and severity of adverse side effects are consistent among reports.
They reported the following figures in the EHA Guidance document, cytokine release syndrome (in severe form) was present in 27-38% of patients. Alloreactivity was another cause of concern because it works to attack the host tissues. Another observable outcome was CAR T cell-related encephalopathy syndrome. Side effects of this include confusion, hallucinations, aphasia, seizures, motor weakness, and cerebral ederma. They also reported other toxicities in pediatric and young adult patients with B-ALL including high fever in 61% of patients, infections (44%), cytopenias (35%), and tumor lysis syndrome (3%). One source confirms that CAR T cell therapies have been used to treat only a few hundred patients to date.
The concern is that these trials are mostly in phase 1, which include a small sample population coupled with short follow-up data. This leaves a lot of uncertainty about the long-term benefits and relapse-free survival rates. There is a long road ahead to determine if individualized CAR T-cell therapies should be mass- produced for the general public as some of these start-up companies are attempting to do.
Issues with Manufacturing Practices
A blood draw that only takes a few minutes to complete, as some of these companies assure, is highly unlikely to produce that amount of blood that is actually needed for T cell therapy. In fact, the actual process of apheresis for existing CAR T cell therapies takes several hours to complete. There are also protocols in place for how a client’s blood should be processed and altered. As one article elaborates, “IND [Investigational New Drug program] outlines a rigid protocol as to how T cells can be collected, stored, and modified for use in an FDA drug candidate or fully approved treatment. As third-party T cell banking is a new phenomenon, it’s unlikely that the infrastructure exists for clinical institutions or commercial enterprises to accept their preserved products.“
There are challenges to scaling out CAR T cell therapies for global use. In an article entitled, “Global Manufacturing of CAR T Cell Therapy,” the authors highlight this point by suggesting, “Until harmonized regulations are established and there is common experience among regions, we can expect a significant level of uncertainty in product development and a greater reliance on subjective judgment by the regulators. Exemplifying this challenge are the different requirements associated with manufacturing that exist among regions. For example, donor screening and testing, traceability and labeling, patient confidentiality, and apheresis requirements can vary widely among countries.”
What is the FDA’S Stance?
It appears that the FDA is agreeance with ISCT. In a statement issued by FDA Commissioner, Scott Gottlieb, he reiterates the position that companies offering patient possibilities without scientific backing and proven results are a danger to the general public and specifically to the patients. He states,
“We’ve seen too many cases of sponsors claiming that cells aren’t subject to FDA regulation just because the cells originated from the same patient to whom the eventual manufactured product is being given. And we’ve seen too many cases of companies making unsubstantiated claims that these treatments prevent, treat, cure or mitigate disease where the products have sometimes led to serious patient harm."
"Patient safety is our first priority. These violative actions create a direct risk to patients. They also create indirect risks by potentially encouraging them to forgo otherwise effective, available treatments, and opt instead for purported treatments that create risks and offer no demonstrated benefits. These kinds of false claims and violative activities also do a tremendous disservice to innovators who are working to legitimately develop safe and effective stem cell therapies by casting doubt across the entire field.”
Several exciting possibilities exist for developing treatments currently being explored in clinical trials for stem cell therapy in regenerative medicine. However, these clinical trials are moving past phase 1 of safety and feasibility and into exploring the actual results and effects in patients. For instance, there are a large number of clinical trials taking place to determine the umbilical cord stem cells’ role in treating cerebral palsy, autism, stroke, multiple sclerosis, diabetes, brain injury, and several other conditions. For a complete list, please visit here.
Furthermore, the ongoing research of the past thirty years has led the FDA to approve umbilical cord blood as a standardized treatment for 80 diseases; including acute lymphoblastic leukemia (ALL), Hodgkin’s lymphoma, and non-Hodgkin’s lymphoma, as well as other types of leukemias and blood disorders. For a complete list, please visit here.
We at Cryo-Cell, alongside other reputable cord blood banks, are on the same team. We share a common goal of safely treating patients and helping families reach triumph over their diseases through the power of umbilical cord blood stem cells. It is our civic duty to spread awareness about cord blood stem cells and the life-saving potential they hold and to inform and educate our audience on the legitimate possibilities that currently exist with cord blood stem cell therapy. Click here to learn more about cord blood banking.
Part of this educational mission is to ensure that the general public understands the difference between careful and proven investigation vs. claims void of any scientific truth. Third-party banks that offer T-cell banking cryopreservation services stand on unethical grounds and contribute nothing but doubt and skepticism to the field of regenerative medicine as a whole. There is substantiated promise in alternative stem cell treatments, but it is not dependent upon adult cryopreserved T- cells.