Scientists have discovered that sodium bicarbonate - also known as baking soda or bicarbonate of soda - can reprogram T cells in leukemia patients to resist the immune-suppressing effects of cancer cells, which can drive leukemia relapse after stem cell transplants.
The work clarifies why patients frequently relapse after transplant and lay the foundation to test sodium bicarbonate as a safe and simple therapy to reduce relapse rates and improve treatment outcomes.
Allogeneic hematopoietic cell transplantation is a form of stem cell transplant that can sometimes cure people with blood cancers such as acute myeloid leukemia (AML). However, complete response rates can be as low as 17% after 100 days, largely because leukemia will frequently return.
There is a pressing need for methods that can boost the anticancer effects of stem cell transplants, but researchers haven't fully understood why donated T cells often fail to finish off tumors.
By studying mouse models of leukemia and T cells from patients before and after transplantation, Franziska Uhl and colleagues found that AML cells suppressed the metabolic activities and the spread of donated T cells by secreting lactic acid, which acidified the cellular environment and interfered with glucose metabolism.
Searching for therapies, the team turned to the antacid sodium bicarbonate and found that a clinical formulation named bicaNorm reversed these suppressive effects on T cells in 10 transplant recipients with relapsed AML.
The authors call for trials with larger groups of patients to better determine the long-term benefits of sodium bicarbonate for recipients of stem cell transplants.
Uhl, F. M., et al. (2020) Metabolic reprogramming of donor T cells enhances graft-versus-leukemia effects in mice and humans. Science Translational Medicine. doi.org/10.1126/scitranslmed.abb8969.