Immortalization of plasma cells leads to Multiple Myeloma (MM). Signaling Lymphocyte Activation Molecule F7 (SLAMF7) is highly expressed on the malignant plasma cells that constitute Multiple Myeloma. The expression of SLAMF7 by MM cells and lack of expression on nonhematologic cells makes SLAMF7 a promising target for chimeric antigen receptor (CAR) T cell therapies for the treatment of MM.
In addition to expression on normal and malignant plasma cells, SLAMF7 is also known to be expressed on a variety of other leukocytes including most natural killer (NK) cells, some CD8+ T cells, a small fraction of CD4+ T cells, NKT cells, some monocytes, and some dendritic cells. Therefore, a CAR targeting SLAMF7 may also eliminate SLAMF7-expressing leukocytes such as NK cells and dendritic cells, which could increase the risk of unwanted side effects from cancer therapies, such as infections. As a way to overcome such unwanted side effects, a “suicide gene” is needed to eliminate anti-SLAMF7 CAR T cells. Furthermore, a suicide gene might also be useful in controlling other types of toxicity such as severe cytokine-release syndrome.
Researchers at the National Cancer Institute (NCI) have created anti- SLAMF7 CAR constructs that allow genetically-modified T cells to express both anti-SLAMF7 antibody and a suicide gene. These CAR constructs allow T cells to specifically recognize and kill SLAMF7-expressing cells, and also allow for on-demand and reliable elimination of anti-SLAMF7 CAR T cells.