Combinatorial use of bridging molecules with AdCAR T-cells targeting AML to eliminate tumor cells
Volta L, Myburgh R, Pellegrino C, et al. Efficient Combinatorial Adaptor-Mediated Targeting of Acute Myeloid Leukemia With CAR T-Cells. Leukemia. 2024; (doi: 10.1038/s41375-024-02409-1)..
Adaptor chimeric antigen receptor (AdCAR) T-cell platforms may allow for better immune-targeting of acute myeloid leukemia (AML), according to researchers. By combining a single CAR construct with different adaptors — which may be full antibodies, antibody fragments, and small molecules — it may be possible to target more than one tumor-associated antigen at the same time, potentially increasing tumor specificity. The biocidal potency of this approach was demonstrated by scientists who developed AdCAR T cells and two adaptor antibody constructs targeting the leukemic antigen CD33 and the cell-of-origin antigen CD117. Combinatorial use of adaptors increased the decoration of target cells and enhanced recognition and activation of CAR T cells, which resulted in greater tumor cell lysis in vitro. The researchers note that therapeutic xenogeneic mouse models suggest that AdCAR T cells can achieve lysis just as effectively as directly targeted CAR T cells.