Identification of unique molecular heterogeneity of human CD79, the signaling component of the human B cell antigen receptor (BCR), and synergistic potentiation of the CD79-targeted therapy of B cell tumors by co-targeting of CD79a and CD79b

• Published in: Leukemia research 2024-01, Vol.136, p.107436-107436, Article 107436
• Main Authors: Seon, Ben K., Okazaki, Morihiro, Duzen, Jill, Matsuno, Fumihiko, Goey, Andrew K.L., Maguire, Orla
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes; CD79a-targeted therapy; CD79b-targeted therapy; Human CD79 heterogeneity; Humans; Lymphoma, Large B-Cell, Diffuse - drug therapy; Mice; Mice, SCID; PD-1-targeted therapy; Receptors, Antigen, B-Cell; Signal Transduction; Synergistic antitumor therapy
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2024.107436

We identified unique molecular heterogeneity of CD79 of human B cell antigen receptor (BCR) that may open a new approach to the ongoing CD79b-targeted therapy of B cell tumors. The primary purpose of the present study is to gain new information valuable for the enhanced CD79-targeted therapy. The molecular heterogeneity of CD79 was identified by sequential immunoprecipitation of BCR by use of anti-CD79b monoclonal antibody (mAb) SN8 and anti-CD79a mAb SN8b. SN8 is the antibody component of polatuzumab vedotin, an anti-CD79b antibody drug conjugate, that has been widely used for therapy of diffuse large B-cell lymphoma (DLBCL). The sequential immunoprecipitation shows that anti-CD79b mAb will be able to react only with a subgroup of CD79 molecules while anti-CD79a mAb will react with another subgroup of CD79 molecules; CD79 is a disulfide-linked heterodimer of CD79a and CD79b. Therapeutic study of SCID mice bearing human B-cell tumor shows synergistic potentiation by co-targeting CD79b and CD79a. Furthermore, simultaneous targeting of PD-1 strongly potentiates CD79a/CD79b-targeted therapy of B cell tumors. Flow cytometry analyses of CD79a/CD79b on malignant B cells of patients may provide a method for selection of the candidate patients for the CD79a/CD79b dual targeting therapy. •Identification of unique molecular heterogeneity of CD79 of human B cell receptor.•Synergy between CD79a-targeted and CD79b-targeted therapy of B cell tumor.•Strong enhancement of CD79-targeted therapy by PD-1-targeted therapy in SCID mice.