Development of CD79B-based Bispecific ADCs

T-cell recruiting bispecific antibodies and antibody fragments have been used to harness the cytotoxic potential of T cells for cancer treatment. CD79B, a component of the B cell receptor (BCR) complex, has been clinically validated by an anti-CD79B antibody-drug conjugate (ADC) as a safe and effective therapeutic target for B cell malignancies. As one of the leaders in antibody engineering, small molecular synthesis, and bio-conjugation, Creative Biolabs provides novel bispecific ADCs targeting CD79B. We believe our services will effectively save the time and cost of your project by taking advantage of our expertise and innovative technology platforms.

The Overview of CD79B

CD79B is the B cell antigen receptor Ig-beta chain. Together with the Ig-alpha chain, also known as CD79A, this cell surface molecule forms a heterodimeric complex CD79 that associates with membrane immunoglobulin (mIgM). CD79B expression is exclusive to B lymphocytes and B cell lymphomas. Depending on the maturation state of the B cell, CD79B can be expressed either in the cytoplasm or on the cell surface. The CD79 receptor complex triggers numerous signaling pathways to mediate B cell development, maintenance, and activation. Most likely due to its function in class II antigen presentation, antibodies that bind CD79B rapidly internalize to the lysosomal compartment.

Fig.1 CD79B and the co-receptor CD19 act as an alternative B-cell signaling module. (He, 2018)

ADC Therapeutics Targeting CD79B

CD79 was considered as a target for antibody therapy when it was first discovered. However, unconjugated anti-CD79 antibodies are not effective under most circumstances. Arming the antibodies with cytotoxic drugs could fulfill the promise of CD79 as a target for antibody therapy. Since CD79B comprise the heterodimeric signaling component of the B-cell receptor, it is an attractive target for the use of ADCs because they are B cell-specific, expressed in non-Hodgkin lymphomas (NHL), and are trafficked to a lysosomal-like compartment as part of antigen presentation. ADCs targeting CD79B were more effective than anti-CD79A ADCs and shown to be very efficacious in preclinical models with both cleavable (SPP-DM1 and MC-vc-PAB-MMAE) and uncleavable linkers. Based on preclinical data, anti-CD79B ADCs with appropriate linker and payload are promising therapeutics for the treatment of NHL.

Bispecific Antibody Targeting CD79B

The development of CD79B-based bispecific antibodies has made great progress in recent years. For example, anti-CD45 x CD79B, anti-CD32B x CD72B bispecific antibody can be potentially used in the treatment of autoimmune disease. Anti-CD3 x CD79B bispecific antibody could be designed for different B cell lymphoma therapy, and researches indicated that this bispecific antibody can induce T cell-dependent cytotoxicity towards CD79B expressing B cells.

What Can We Do for You?

Based on our in-depth and comprehensive research, CD79B has the potential of being a highly effective bispecific ADC target, and drug conjugates targeting this receptor could have significant clinical potential. Creative Biolabs has been involved in the development of ADCs for many years and we are committed to completing your project with high quality. We have constructed different target combinations for CD79B-based bispecific ADCs development, including CD79B x CD3, CD79B x CD32B and CD79B x CD45. For any specified combination, we would like to discuss with you further to obtain the best solution. Please do not hesitate to contact us for more information.

Reference

1. He, X.; et al. Continuous signaling of CD79B and CD19 is required for the fitness of Burkitt lymphoma B cells. The EMBO journal. 2018, 37(11).

For Research Use Only. NOT FOR CLINICAL USE.