Novel Ligand-Based CAR-NK Cell Therapy for the Treatment of B Cell Malignancies
2021 Harrington-MSTP Scholar
B-cell malignancies encompass many different types of cancer, such as acute lymphoblastic leukemia (ALL), non-Hodgkin lymphomas (NHL), chronic lymphocytic
leukemia (CLL) and multiple myeloma (MM). Chimeric antigen receptor (CAR) T-cell therapy has proven effective for the treatment of relapsed/refractory B-cell malignancies, but the high cost, complex manufacture, and adverse effects associated with CAR-T therapy leaves room for underexplored cellular immunotherapies, such as CAR-NK cells.
“Unlike CAR-T cells, the CAR-NK concept allows you to take natural killer (NK) immune cells from a healthy donor and genetically modify, expand and freeze them, and then quickly deliver them to cancer patients when they need them. In essence, this is an ‘off the shelf' treatment,'” says Mr. Derek Wong.
B-cell activating factor (BAFF) is a protein that normally helps regulate B-cell development and survival, but BAFF receptors are also expressed by numerous B-cell cancers. Mr. Wong's innovation combines the BAFF-CAR construct the lab already validated in T cells with NK cells to create BAFF CAR-NK cells.
“If the cancer cell expresses any of the B-cell activating factor receptors, our BAFF construct CAR-NK cells will target them,” Mr. Wong says.
With Harrington support, Mr. Wong and his team have further modified their BAFF-CAR construct to make them more specific for NK cells. They have narrowed down their
designs to two novel, promising provisional patent candidates that have been effective against cancer cell lines in culture. “We hope our approach can be used to treat
relapsed B-cell cancers, re-inducing remission and prolonging patient survival,” Mr. Wong says.