Health
CAR T Drives Acute Myeloid Leukemia to Preclinical Trials-ScienceDaily
Researchers at Massachusetts General Hospital (MGH) have found that new treatment strategies that may bring the life-saving effects of chimeric antigen receptor T cell therapy (CAR T) to patients with the most common forms of acute myeloid leukemia (AML). Was developed. Leukemia in adults.
This method involves a combination of drug therapy to increase the number of targets on tumor cells and an engineering approach to help the therapy adhere more firmly and permanently to those targets.
They describe their work in a study published online in a journal cancer cell.
CAR T therapy has revolutionized the care of patients with advanced cancers of the blood system. This involves harvesting patient T cells, an important component of the immune system, and genetically modifying them to recognize specific targets (antigens) on the surface of cancer cells. The cells then proliferate in the laboratory and are returned to the patient’s bloodstream, where the immune response that kills the tumor is enhanced.
CAR T therapy relies on the ability of T cells to identify antigens that are specific to cancer cells or that are much more abundant in normal cells than in malignant cells.
For lymphocytic malignant tumors such as acute lymphoblastic leukemia and white blood cell B-cell lymphoma, targeting the tumor can deplete a population of normal antibody-producing B cells, but clinicians are immune. Replacing globulin can compensate for the loss of normal cells. B cells are usually made.
“In contrast, the normal counterpart of acute myeloid leukemia is the bone marrow cells involved in the fight against infection. Unfortunately, we cannot live very long without them,” said lead author Mark B. Dr. Like Medicine, a researcher in cell immunotherapy, said. Program at MGH Cancer Center,
Previous attempts to treat advanced AML with CART therapy have been hampered by the lack of appropriate antigens and the “off-target” effect of treatment when killing a large number of healthy normal and cancer cells.
Leick, along with senior researchers Marcela V. Maus, MD, PhD, director of cell immunotherapy at the MGH Cancer Center, and colleagues, began with a CART construct against an antigen called CD70 that is more abundant than present on AML cells. I did. Normal myeloid cells. CAR T alone had a modest effect on AML in animal models, but when combined with the FDA-approved AML drug azacitidine, it increased the number of CD70 antigens on the surface of cancer cells.
“By combining the two, we were able to show that the death of tumor cells was improved,” he says.
Moreover, unlike most CARs that use mouse-derived antibodies to target antigens that can trigger unwanted immune responses, the CAR used in this study is a ligand that binds tightly to the antigen. It relies on a known type of natural molecular binding, thereby avoiding the possibility of the immune system recognizing the tumor-killing mechanism as a foreign body and trying to reject it.
Finally, they overcame the problem that plagued older versions of CAR T cells targeting AML.
“AML cells secrete proteinase, an enzyme that is essentially capable of decapitating CAR T cells, so we have identified where the cleavage takes place and changed that region so that CAR T cells are firmly on the tumor. It’s more effective than binding and killing. “
“We are excited about the therapeutic potential of this new CAR T cell product and hope to be able to provide it to patients with acute myeloid leukemia immediately,” says Maus.
This study was funded by grants from the National Institutes of Health, the National Science Foundation, the Swiss National Science Foundation, and the Gabriel Angel Foundation.
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