Development of Chimeric Antigen Receptors Targeting Multiple Myeloma

Division Of Basic Sciences - Nci

Investigators

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Abstract

An important focus of my work is development of chimeric antigen receptor T cell therapies for multiple myeloma, which is a usually incurable malignancy of plasma cells. A major obstacle to development of CAR-expressing T-cell therapies for multiple myeloma is the lack of suitable target antigens. Anti-BCMA CARs: I have recently designed and constructed two CARs that specifically recognize B-cell maturation antigen (BCMA). BCMA has a very restricted expression pattern in normal tissues, but BCMA is expressed on the malignant plasma cells of multiple myeloma.7 The BCMA ?specific CARs that I have constructed specifically recognize multiple myeloma cell lines in functional assays in vitro. An extensive analysis of BCMA expression in normal human tissues by immunohistochemistry and quantitative PCR has been conducted. Except for expression by normal plasma cells, BCMA expression was not detected in nomal human organs by immunohistochemistry. The next step in developing anti-BCMA CARs will be testing in animal models. Potentially, anti-BCMA-CAR-transduced T cells could be assessed in clinical trials. Other CARs targeting multiple myeloma: In addition to developing anti-BCMA CARs, I aim to develop CARs that target other antigens that are expressed by multiple myeloma cells but not normal essential tissues. Some promising candidate antigens have been identified, and initial evaluation of these antigens has begun.