Exploring CD19-targeted Immunotherapy Strategies for human B-cell lymphoma

Abstract

B-cell lymphomas (BCLs) comprise approximately 40 subtypes resulting from mature B-cells' malignant transformation. BCLs are treated differently based on the type and stage of the lymphoma. Multiple therapeutic options exist, including chemotherapy, immunotherapy, radiation therapy, targeted therapy, and stem cell transplantation. Among them, targeted therapy has shown great potential for safer and more effective treatment. Targeted therapies include monoclonal antibodies and nanobodies, CAR-T cell therapies, and Bispecific T-cell engager (BiTE), which operate in diverse ways by targeting a number of molecules including CD79b, CD20, CD30, CD52, and CD19. CD19 is an immunoglobulin superfamily transmembrane glycoprotein of type I which is necessary for setting intrinsic B-cell signaling thresholds by tempering both receptor-dependent and receptor-independent signaling. According to the limitations of conventional therapies and other targets, it seems that CD19 is a proper target for lymphoma. There are several FDA-approved anti-CD19 CAR-T cells such as Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel, and Anti-CD19 Monoclonal Antibodies (mABs) such as Loncastuximab Tesirine and Tafasitamab, for which more than a few clinical trials have shown trustworthy results. Blinatumomab is the first FDA-approved antibody produced using BiTE technology which has shown good benefits in B-cell ALL treatment clinical trials. Single-domain antibodies (sdAb) or nanobodies, are the nanoscale VHH fragments of heavy chain-only antibodies (HcAbs) and have been utilized in conjunction with CAR T-cells, yielding promising outcomes. In this review, we aimed to discuss CD19 as an auspicious therapeutic target for lymphoma. Moreover, we talked about different treatment options regarding CD19 targeting, along with the relevant clinical studies, for each of which, the efficacy, safety, and limitations were elaborated.