Patterson MT, Khan SM, Nunes NS, et al. Murine Allogeneic CAR-T Cells Integrated Before or Early After Posttransplant Cyclophosphamide Exert Anti-Tumor Effects. Blood. 2022; (doi: 10.1182/blood.2022016660).
Scientists now believe it possible, with the right timing, to achieve anti-tumor effects by directly integrating chimeric antigen receptor (CAR) T-cells and allogeneic hematopoietic cell transplantation (allo-HCT). The combination approach had previously been dismissed based on a presumption that allogeneic CAR T-cells would induce graft-versus-host disease (GVHD) under these circumstances. Using a murine model, researchers discovered that infusing allogeneic CAR T-cells before post-transplantation cyclophosphamide (PTCy) or immediately after effectively cleared leukemia without increasing toxicity. The strategy neither worsened cytokine release syndrome from the allo-HCT, nor did it disrupt PTCy-mediated prevention of GVHD. Investigators identified the optimal range for integrating allogeneic anti-CD19 cells as the day before PTCy to as many as 5 days after. More favorable clinical outcomes — including earlier CAR T-cell expansion, higher phenotypic CAR T-cell activation, and more cytotoxic CD8+CAR T cells — were observed with infusion on the day before PTCy as opposed to on day 5. CAR T-cell therapy was still effective on days 9 and 14, but less so. The study offers hope for novel interventions coupling the benefits of CAR T and allo-HCT, which are limited by high levels of relapse when pursued independently.
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