Researchers have developed a novel B cell-activating factor (BAFF) ligand-based chimeric antigen receptor (CAR) T-cell therapy capable of binding to all the three receptors expressed on mature B -cells. Results of this investigation were published in the Journal Nature Communication.
Immunotherapy such as CAR T-cell therapy has been at the forefront of cancer treatment for the past few years. However, disease relapse is often observed due to the loss of CAR-specific antigens. Thus, it is essential to develop alternative treatment strategies to target multiple markers on tumour cells. One such attractive target is the three receptors on B-cells, BAFF-R, BCMA, and TACI. At least one receptor is consistently found to be expressed on all the B-cell cancers. The researchers utilised this property and designed ligand-based CAR-T cells to target all three BAFF receptors. Experiments showed that BAFF CAR-T cell therapy is highly effective in targeting multiple-B cell cancers in vitro and in vivo.
Overall, the researchers show that the BAFF CAR-T cells are both functional and specific in targeting the three BAFF receptors expressed by multiple B cell cancers. Moreover, they demonstrated that BAFF CAR T-cells exerted potent cytotoxicity against mantle cell lymphoma (MCL), multiple myeloma (MM), and acute lymphoblastic leukaemia (ALL) cell and animal models. Importantly, CAR-T cells targeting CD19 kill both early and mature B cells; the BAFF CAT-T cells do not target early B cells as these cells do not express any of the three receptors.
Wong DP, Roy NK, Zhang K, Anukanth A, et al. A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers. Nat Commun [Internet]. 2022;13(1):217. Available from: https://doi.org/10.1038/s41467-021-27853-w