Discovery of novel targets for diffuse large B-cell lymphoma

The newly emerging CD19-targeted Chimeric Antigen Receptor T-cells (CAR-T) therapy has revolutionized the treatment of advanced diffuse large B-cell lymphoma (DLBCL) and achieved a functional cure in some patients. However, a majority of patients suffer relapse. A major pathway for tumor relapse is the loss of the target antigen, CD19, on the cancer cell surface, essentially making them invisible to the therapy. Consequently, new targets are required for the continued treatment of relapsed patients. Facing this dilemma, we hypothesized that a systematic search of the human genome may reveal more novel targets of DLBCL with characteristics similar to CD19. These include high expression in DLBCL and other B-cell tumors, but minimal expression in normal tissues. To test this hypothesis, we used several well-annotated public genomic and proteomic databases and carried out in-depth screening to pinpoint optimal new targets for DLBCL. Our study uncovered several new targets that have not been extensively pursued in the public domain, such as CD79A and TNFRSF13C. Based on our refined criteria for target evaluation, we finally concluded that CD79A represents the most ideal novel target for DLBCL and potentially other B-cell tumor types. This target should be explored as the antigen of next-generation CAR-T therapy that has the potential to save and extend the lives of patients.