B-cell maturation antigen (BCMA) is a potential target antigen in multiple myeloma due to its highly selective expression in malignant plasma cells. BCMA-targeted CAR T-cell therapy has been proven to be effective in patients with multiple myeloma. Despite that complete remission level reaching around 60-86%, a subset of patients still experience tumor relapse. Tumor escape due to low antigen density and limited efficiency in single-targeting BCMA CAR. In this webinar, Dr. Maria Themeli showed how to overcome low antigen density and improve CAR-T cell persistence with multi-targeting and co-stimulation through increasing synaptic avidity with the z-Movi.
Key learning points:
- Dual-targeting with CD38 co-receptor is demonstrated to improve BCMA CAR sensitivity and efficacy against multiple myeloma.
- Incorporating two costimulatory signals, CD28 and 4-1BB, into the dual-targeting approach helps to elicit faster and stronger cytotoxic capacity, enhance in vivo persistence, and drive higher expansion rate
- The power of cell avidity as a functional biomarker for improved CAR T design in preventing tumor relapse.
