CAR T-Cells for T-cell Lymphoma

Abstract

Introduction Developing CAR T-cells for T-lineage malignancies requires minimizing fratricide of engineered T-cells and mitigating the risk of T-cell aplasia, which may be caused by the off-tumor activity of CAR T-cells. We have developed and optimized for clinical evaluation a CAR targeting pan-T-cell antigen CD5, which is highly expressed in peripheral T-cell lymphoma. Expression of an optimized CD5 CAR produces only transient and limited fratricide as T-cells rapidly internalize and degrade CD5 protein in a CAR-dependent manner. Resulting CD5 CAR T-cells are fratricide-resistant and produce strong anti-tumor activity in mouse xenograft models of human T-cell malignancies.1 Based on this preclinical work, we initiated a Phase I clinical trial at Baylor College of Medicine with autologous CD5 CAR T-cells in patients with refractory or relapsed T-cell malignancies as a bridge to allogeneic HSCT (NCT03081910).