Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas

Area of Science:

• Immunology
• Oncology
• Cell Therapy

Background:

• Chimeric antigen receptor (CAR) T cells targeting CD19 are effective against B-cell malignancies but face resistance due to antigen loss.
• CD79b is a pan B-cell antigen widely expressed in most B-cell lymphomas, making it a potential target for overcoming resistance.

Purpose of the Study:

• To develop and evaluate a novel CAR T-cell therapy targeting CD79b for B-cell lymphomas.
• To assess the efficacy and specificity of CD79b-targeting CAR T cells in preclinical models.

Main Methods:

• Generated a novel anti-CD79b monoclonal antibody and derived a single-chain variable fragment.
• Constructed various CD79b-targeting CAR molecules with different domains and transduced them into primary T cells.
• Tested CAR T-cell activity in vitro and in vivo using B-cell lymphoma models, including CD19-negative and patient-derived tumors.

Main Results:

• The anti-CD79b antibody was highly specific for human CD79b.
• A CD79b CAR with CD8α hinge/transmembrane, OX40 co-stimulatory, and CD3ζ signaling domains demonstrated superior antitumor efficacy.
• CD79b CAR T cells showed robust proliferation, cytokine production, cytotoxicity against CD19+ and CD19- lymphoma cell lines, and eradicated tumors in vivo without significant tonic signaling or exhaustion.

Conclusions:

• The novel CD79b CAR T-cell therapy exhibits robust antitumor activity against B-cell lymphomas.
• These findings support the initiation of a phase 1 clinical trial for patients with relapsed or refractory B-cell lymphomas.