What’s that word mean?!
An intro to allogeneic cell therapy and why it matters
Hope Biosciences Research Foundation (HBRF) conducts sometimes simultaneous research in the same disease or injury condition, exploring both autologous cell therapy (using a patient’s own stem cells) and allogeneic therapy (using carefully selected donor cells). At the time of this writing, HBRF is actively enrolling participants in allogeneic research in Parkinson’s Disease and “Long Haul” COVID, having recently completed autologous protocols in both conditions, which means we spend a lot of time on the phone explaining terms to patients, families, caregivers, and medical practitioners. Have questions, yourself? Here’s what you need to know about allogeneic cell therapy and your possible healthcare future.
What is allogeneic cell therapy?
“Allogeneic” means, in essence, “something from distinct individuals in the same species.” Allogeneic mesenchymal cell therapy, then, means using adult stem cells from one human for therapeutic effect in another human.
HBRF conducts allogeneic research in part because allogeneic therapies are the fastest way to get cells to people who need them in cases of catastrophic injury, such as spinal cord or brain injury; sudden systemic illness, such as COVID; unexpected chemical exposure, such as in biological or chemical warfare; or for prevention of possible pathogens. Development of autologous treatment in such circumstances requires access to the patient to harvest adipose tissue (in HBRF-run protocols, that means approximately a tablespoon of fat from the abdominal area by a licensed dermatologist), then approximately 8 weeks to create a cell bank, and more days to create an initial treatment. Getting access to the patient can create its own set of challenges, in addition to time, depending on fragility of their condition at the time of injury or sudden illness. Allogeneic therapies circumvent these logistical challenges because a treatment from donor cells can be grown fresh in a matter of days; there is additional potential to have cells always “ready to go” in high-risk environments. HBRF believes allogeneic cell therapy has strategic value as a sole therapy, and as a mechanism for treatment close to the time of injury or illness, while autologous treatments are cultured.
How are allogeneic studies run at HBRF?
There is no difference in quality of patient experience between allogeneic and autologous therapies at HBRF. Cells studied at HBRF are cultured and cared for to the same high standard and regulated the same way, whether treatments are autologous or allogeneic. Potential participants in FDA-authorized allogeneic protocols at HBRF are screened and selected in the same manner and through the same process as any other. Stem cell donors themselves are carefully screened and selected. Treatments contain the same number of cells in both autologous and allogeneic protocols, as agreed to with the Food and Drug Administration (FDA) — typically 200 million cells per dose in adults (pediatric protocols may dictate lower volume doses, in recognition of the patient’s dramatically smaller physical size). Philosophical and ethical considerations of allogeneic mesenchymal cell therapy are no different than in other established medical transplantation procedures, such as a blood transfusion or organ transplant.
One difference that speaks to the potential of allogeneic therapies to increase access to biotechnology is that at HBRF, allogeneic protocols have no charge to patients. Treatment is always free at HBRF to ensure integrity of data collected, but autologous protocols typically require patients to enter into private agreement to bank their cells, assuming responsibility for the banking fee and any decisions about how long to maintain their personal cell bank. Allogeneic research removes all fiscal barriers to participation, opening access to individuals but also dramatically expanding the potential patient population and diversifying participant demographics. Such an evolution in clinical research participation carries exciting social and technological promise.
Considering patient populations, allogeneic therapies also create an opportunity to treat individuals with certain disease histories, such as syphilis or certain forms of hepatitis, whose cells cannot be safely stored due to high risk of contamination. Assuming a given protocol does not exclude these same conditions from participation, allogeneic therapies provide a path to participation and treatment where none previously existed.
Is it safe?
The allogeneic research currently conducted by HBRF are FDA-authorized Phase II clinical trials, a stage in the four phases of clinical research dedicated to establishing efficacy, or how well a given treatment “works,” in a small population. By authorizing a Phase II study, a patient knows FDA considers safety of the drug already established and proven — if FDA thought there a high likelihood a given treatment would prove unsafe, they would require another Phase I, or even an animal trial, before allowing the drug to be administered to humans. Thus far, allogeneic therapies have the same safety profile as autologous treatments. Mesenchymal stem cells (MSCs) have immunosuppressive properties and low immunogenicity, which means they elicit little immune response when compared to allogeneic work with other cell types.[1] As early as 2005, researchers concluded MSCs are “a highly regulated self-renewing population of cells with potent mechanisms to avoid allogeneic rejection.”[2] Work in the intervening decades has only confirmed that initial conclusion, adding the credibility of an ever-increasing body of confirming data.
In conclusion:
A growing suite of allogeneic research represents what HBRF hopes is a significant contribution in increasing regulatory acceptance of allogeneic adult cell therapies. Allogeneic therapies, with their dramatically reduced costs for manufacturing stem cells to a comparable safety profile as autologous cell therapies, and with equal or better potential for scalability, represent a promising way for ensuring equitable access to cell therapies in the future.
[1] For more, see Zhang, et. al’s “The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy,” Stem Cell Research & Therapy, 2015.
[2] See Ryan, et. al’s “Mesenchymal stem cells avoid allogeneic rejection,” Journal of Inflammation, 2005.
