4th-generation B-cell maturation antigen CAR-T (BCMA-4-1BB-CD3zeta-IL-15)

4th-generation B-cell maturation antigen CAR-T (BCMA-4-1BB-CD3zeta-IL-15) is an investigational chimeric antigen receptor (CAR) T-cell therapy designed for the treatment of multiple myeloma. This cell-based gene therapy is engineered via lentiviral transduction to express a CAR targeting the B-cell maturation antigen (BCMA), which is highly expressed on malignant plasma cells. The construct incorporates a 4-1BB costimulatory domain and a CD3ζ signaling domain to drive T-cell activation and survival. Uniquely, it is further modified to produce soluble interleukin-15 (sIL-15), a cytokine intended to enhance T-cell expansion, promote a central memory phenotype, and improve tumor infiltration. Preclinical studies in NSG mouse models have demonstrated that while this 4th-generation construct provides rapid and potent antitumor activity, the high levels of cytokine production were associated with significant toxicity, highlighting a need for optimized cytokine expression to balance therapeutic efficacy and safety.

Other names

4th-generation BCMA CAR-TIL-15-producing BCMA CAR-T cellsIL15-producing BCMA CAR-T cellsIL 15-producing BCMA CAR-T cellsBCMA-4-1BB-CD3ζ-IL-15