Numerous approaches are under investigation to increase CAR T-cell efficacy in solid tumor settings, reduce CAR T-cell relapse rates, and reduce the toxicity associated with CAR T-cell therapy. This study highlights the potential of G 4S-displaying CAR T cells to be redirected to engage alternative tumor-associated antigens (TAA). The cytolytic activity of CAR T-cells was redirected to different tumor antigens by changing the BsAb in a dose-dependent manner. We demonstrated that the BsAb can bridge CAR T cells to tumor cells and potentiate CAR T-cell activation, proliferation, and tumor cell cytolysis. Herein, we described a novel CAR T-cell adapter platform that relies on a bispecific antibody (BsAb) targeting both a tumor antigen and the GGGGS (G 4S) linker commonly used in single-chain Fv (ScFv) domains expressed on CAR T-cell surfaces. Adapter CARs allow simultaneous or sequential targeting of multiple tumor antigens, control of immune synapse geometry, dose control, and the potential for improved safety. To address this limitation and to add a further level of tunability and control to CAR T-cell therapies, adapter or universal CAR T-cell approaches use a soluble mediator to bridge CAR T cells with tumor cells. Nevertheless, the occurrence of relapse due to antigen escape or heterogeneous antigen expression on tumors remains a challenge for first-generation CAR T-cell therapies as only a single tumor antigen can be targeted. Tell a Story day is here! Here is the conclusion to the super-exciting interactive story that we wrote together.The success of chimeric antigen receptor (CAR) T-cell therapy against hematologic malignancies has altered the treatment paradigm for patients with these diseases. ![]()
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