Chimeric Antigen Receptor T-cell therapy is also known as CAR-T therapy. These cells are key components in the immune system. CAR-T therapy involves harvesting a patient’s cells, then genetically altering them to recognize a specific antigen on the surface of the cancer cell. These cells are then expanded and injected back into a patient’s bloodstream. The goal is for these modified CAR-T cells to attack the tumor cells.
The CAR-T therapy relies on the ability of the T cells locating the right targets (antigens) that are unique to the cancer cell. Most lymphoid cancers generate from white blood cells. Treatment can kill normal white blood cells in the process of destroying cancer cells, but doctors can compensate by replacing immunoglobulins that B cells normally make.
This is not the case with AML and why it has proven so difficult to treat. This cancer involves myeloid cells (not white blood cells), which are used to fight infection. Previous attempts to treat AML with CAR-T therapy have not proven effective because the right antigen can not be found and too many healthy ‘normal’ cells are destroyed.
The researchers at Massachusetts General Hospital have developed a new strategy in the treatment of AML, the most common form of leukemia in adults. This new information provides a more effective and potent use of CAR-T cell therapy in patients. “The method involves a combination of drug therapy to expand the number of targets on tumor cells, and an engineering approach to help the therapy adhere more tightly and durably to those targets.”
Researchers started with an antigen called CD70 (it can be found in larger numbers on AML cells than on regular myeloid cells). Then the antigen was combined with the drug azacitidine to increase the number of CD70 targets found on the surface of the cancer cells. This combination provided promising results in the killing of tumor cells.
“In addition, unlike most CARs that use antibodies derived from mice to target the antigen, which can cause an unwanted immune reaction, the CAR used in this study relies on a kind of a natural molecular bond known as a ligand to bind tightly to the antigen, thereby avoiding the possibility that the immune system would recognize the tumor-killing machinery as foreign and try to reject it.”
AML cells produce an enzyme, a proteinase, that is able to decapitate the CAR-T cell. Researchers localized where the cut takes place, and modified that area. Now the CAR-T cells bind tighter to the tumor and can kill it more successfully. “Our CD8 hinge and transmembrane-modified CD70 CAR-T cells are less prone to cleavage, have enhanced binding, and increased expansion, leading to more potent activity. This enhanced CD70-targeted CAR is a promising candidate for further clinical development.”
The researchers state, “We are excited for the therapeutic potential of this new CAR T cell product, and hope that we can offer it to patients with acute myeloid leukemia soon.”
about the author
Lisa Foster is a mom of 3 daughters, a puzzle lover, writer and HealthTree advocate. She believes in the mission of the foundation and the team that builds it forward. She calls Houston, Texas home.