CD79b: The Core Target in B-Cell Signaling and Therapeutic Innovation

February 24,LTZ Therapeutics announced that its potential "first in class" myeloid cell engager LTZ-301 has received clinical tacit approval from the U.S. FDA for the treatment of relapsed or refractory non-Hodgkin lymphoma (r/r NHL).LTZ-301 is a novel bispecific antibody that acts as a myeloid cell engager, enhancing Fc-γ receptor (FcγR)-independent ADCC effects to target and eliminate CD79b-positive B cells. CD79b is a unique tumor antigen receptor that is highly expressed in B-cell malignancies.

Introduction to CD79b Target

CD79 is a transmembrane protein that binds to the B-cell receptor (BCR) as a complex and generates signals after the BCR recognizes an antigen. CD79 consists of two distinct peptide chains, known as CD79a (Iga) and CD79b (Igβ), which form a heterodimer on the B-cell surface through disulfide bonds and participate in signal transduction in B cells.

CD79b is a key component of the B-cell surface immunoglobulin (Ig) complex, belonging to the CD79 family and primarily expressed from the pre-B cell to mature B cell stages. It is responsible for transmitting B-cell receptor (BCR) signals to regulate immune responses and antibody production. Its N-terminal tyrosine kinase domain can recruit and activate downstream signaling molecules such as Syk, playing a central role in B-cell development, proliferation, and differentiation. Based on the characteristic expression of CD79b on B cells, it has become one of the most effective targets for abnormal B-cell proliferation.

Figure: CD79b-Mediated Signaling Pathway in B Cells

Polatuzumab Vedotin, developed by Roche in Switzerland, is an antibody-drug conjugate (ADC) targeting CD79b. It delivers the potent anti-mitotic agent monomethyl auristatin E (MMAE) to B cells, killing malignant B cells.

The drug was approved by the U.S. FDA in 2019 (POLIVY® polatuzumab vedotin) for untreated, relapsed, or refractory diffuse large B-cell lymphoma (DLBCL) in adult patients. In China, the drug was approved for marketing by the NMPA in January 2023 (优罗华® 维泊妥珠单抗).

PRV-3279 is a humanized bispecific antibody targeting CD32B and CD79B on the surface of B cells, with the potential to treat B cell-mediated autoimmune diseases and prevent or reduce immunogenicity associated with biological therapies.

At the beginning of 2021, Huadong Medicine obtained the exclusive clinical development and commercialization rights in Greater China for two clinical indications of PRV-3279, a bispecific antibody product under research by Provention Bio. The application for Phase 2 clinical trials for the treatment of moderate to severe systemic lupus erythematosus (SLE) was approved in China in April 2023. After the approval of Polivy, its sales increased year by year: $181 million in 2020, $326 million in 2021, $591 million in 2022, and $946 million in 2023.

SHR A1912 is a CD79-targeted drug independently developed by Hengrui Medicine.bSHR-A1912, an ADC targeting CD79b, ranks second globally in the R&D progress of ADC projects with this target.

Previously, the clinical trial application for SHR-A1912 for the treatment of B-cell non-Hodgkin lymphoma has received tacit approval from the U.S. FDA. The clinical trial applications for SHR-A1912 as a single agent and in combination with immunochemotherapy for the treatment of B-cell non-Hodgkin lymphoma have also successively obtained approval from the NMPA, and it has currently entered Phase II clinical trials. No clinical data on SHR-A1912 has been reported yet, but if subsequent clinical outcomes are positive, it holds certain potential for overseas expansion.

LTZ-301 is a novel myeloid engager bispecific antibody that eliminates CD79b+ B cells by redirecting monocytes and macrophages to CD79b+ B cells, enhancing non-Fc-gamma receptor (FcγR)-dependent antibody-dependent cellular phagocytosis (ADCP). Preclinical studies have shown that LTZ-301 exhibits potent pharmacological effects in both in vitro and in vivo studies, with a favorable safety profile.

 CD79b As the main signal transduction molecule of B cells, it is of great significance for revealing the role of B cells in immune responses and pathological states. From basic research to clinical applications, CD79b The discussion will provide new ideas and methods for the diagnosis and treatment of B cell-related diseases.

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