A method for selecting distinct T cell populations in order to generate more effective CAR-T cells.
Chimeric antigen receptor T cell (CAR-T) therapy is an emerging branch of cancer immunotherapy. It involves extracting a patient’s own T cells, engineering them to express an antigen-specific receptor to target tumor cells, and transferring them back into the patient. Currently, CAR-T therapy is only approved for certain forms of non-Hodgkin’s lymphomas, one of the top ten most common cancers in the US and has a success rate of 30-40% for lasting remission. Additionally, patients with certain types of aggressive cancer who have experienced multiple relapses with first-line treatments may qualify for CAR-T cell therapy. In order to advance these therapies and potentially aid a larger population of patients, ongoing efforts are needed to improve effectiveness of CAR-T cell therapies.
T cells experience “basal” T cell receptor signaling in response to self-antigens (antigens normally found in the body and not from an invading pathogen). The strength of this signal varies from cell to cell but is an intrinsic and stable characteristic. Researchers at Emory have discovered a subset of T cells with low reactivity to self-antigens, resulting in increased reactivity to foreign antigens. Inventors then identified cellular markers that reflect this strength of a T cell’s basal signal. The level of the cellular marker expression corresponds to the strength of the T cell’s basal signal. Based on preliminary data we predict selection of T cells derived from less self-reactive T. cells would be superior and function against their targets. Using such selection methods could be used to generate more efficient CAR-T cell therapies.
Proof of concept experiments have been conducted using murine CD4+ T cells.