Transcriptional changes associated with treatment of Chimeric Antigen Receptor (CAR)-T cells with a novel CAR-Enhancer construct

We have developed an antigen based platform (CAR-Enhancer) that involves the fusion of a target antigen (e.g., BCMA) with a low affinity enhancer molecule (e.g., IL-2). This method allows for the precise targeting of CAR-T cells and facilitates the preferential delivery of immune-modulating agents post infusion.In this study, we look at the transcriptional changes associated with treating BCMA-CAR-T cells with the BCMA-weakaffinity IL2 CAR-Enhancer. As a control, we included rested CAR-T cells, CAR-T cells treated with wild type IL2, CAR-T cells treated with mutated IL2 fused to an irrelevant protein and CAR-T cells treated with a BCMA minibody (The CAR-Enhancer lacking the mutated IL2 portion). We also included CAR-T cells lacking the intracellular signaling domain treated with the CAR-Enhancer. We sorted and sequenced CD4 and CD8 CAR-T cells separately and included two timepoints post treatment (2 hours and 22 hours)