New research from Memorial Sloan Kettering Cancer Center (MSK) developed CAR T cells that target two acute myeloid leukemia-specific antigens; shed new light on a genetic element called LINE-1, opening the door to new treatments; identified a key regulator of blood stem cell fate; and found an immunotherapy technique using antibodies that target CD47 shows promise in mice.
CAR T Cells that target two antigens treat AML with minimal toxicity
Acute myeloid leukemia (AML) has so far resisted treatment with chimeric antigen receptor (CAR) T cell therapy. One reason is that AML cells have different target antigens from cell to cell within the same patient. In addition, AML cells share antigens with normal blood stem cells, which give rise to many blood cells, including immune cells. Conventional CAR T therapy targeting AML could inadvertently weaken the entire immune system, requiring the patient to have a "rescue" bone marrow transplant.
Now, physician-scientist Michel Sadelain, M.D., Ph.D., a pioneer in CAR T cell research, has developed an ingenious tactic for solving this problem. Working with senior research scientist Sascha Haubner, M.D., Sadelain's team designed so-called cooperative CAR T cells that detect two AML antigens — ADGRE2 and CLEC12A — at once. This helps the CAR T cells eliminate AML cells while sparing normal blood stem cells and causing severe effects. A clinical trial using this approach is set to begin at MSK soon under the direction of hematologic oncologist Jae Park, M.D
