Analysis of polyfunctionality for enhanced BAFF-R CAR T-cell therapy for hematologic malignancies

Area of Science:

• Immunotherapy
• Oncology
• Cellular Therapy

Background:

• Chimeric antigen receptor (CAR) T-cell therapy shows promise for cancer eradication.
• Therapeutic success depends on CAR T-cell functional capacity, including expansion and persistence.
• CD19 CAR T-cell polyfunctionality, measuring cytokine production, proliferation, and cytotoxicity, correlates with clinical outcomes.

Purpose of the Study:

• To optimize a single-cell platform for assessing CAR T-cell polyfunctionality.
• To evaluate B-cell-activating factor receptor (BAFF-R) CAR T-cells against a novel target.
• To validate the platform using CD19 CAR T-cells and apply it to a patient with non-Hodgkin lymphoma.

Main Methods:

• Developed and optimized a single-cell platform for CAR T-cell polyfunctionality.
• Manufactured BAFF-R CAR T-cell products from healthy donors and validated with CD19 CAR T-cells.
• Applied the assay to autologous BAFF-R CAR T-cell product from a patient with relapsed non-Hodgkin lymphoma.

Main Results:

• Distinct qualitative differences observed between BAFF-R and CD19 CAR T-cells regarding cytokine profiles and target antigen density.
• CD19 CAR T-cells generally exhibited lower polyfunctionality indices compared to BAFF-R CAR T-cells.
• The assay detected robust polyfunctionality indicators in the patient's BAFF-R CAR T-cells, correlating with expansion and durable complete remission.

Conclusions:

• The optimized single-cell platform effectively assesses CAR T-cell polyfunctionality.
• BAFF-R CAR T-cells show promising indicators of efficacy in a patient with relapsed non-Hodgkin lymphoma.
• Further analysis in additional patients is needed to fully elucidate BAFF-R CAR T-cell fitness, toxicity, and clinical outcomes.