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.

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.

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Copyright © 2024. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no conflict of interest. Hybridomas of anti-CD79 mAbs SN8, SN8a and SN8b that had been generated in our laboratory at Roswell Park Cancer Institute (RPCI) were licensed to Genentech and Genentech researchers used SN8 to generate polatuzumab vedotin (PV). The license agreement between RPCI and Genentech/Roche expired. SN8 (hybridoma clone 3A2–2E7) was also licensed to BD Biosciences and other companies for diagnostic or research use.