TCR-like Antibodies for B Cell Malignancies. Can They Overcome Resistance to Antibody-Based CAR T Cells?
Chimeric antigen receptor (CAR) T cells directed at the CD19 surface protein are an effective treatment for refractory B cell leukemia and lymphoma.
Despite high response rates, many patients will experience relapse with loss of CD19 at the time of relapse
TCR-like (TCRL) antibodies are designed to bind a peptides presented in the context of an HLA molecule, and therefore expand the target repertoire of tumor associated antigens to include intra-cellular proteins. In this study we aimed to address the phenomenon of CD19 negative relapse following CAR T cell therapy using the TCRL approach. We have successfully isolated TCRL antibodies with specific binding to a complex of HLA-A2 and CD19-derived peptides. TCRL-based CARs were generated and exhibited effective killing of multiple B cell malignancies, including cells with loss of surface CD19. This study provides proof-of- concept for the targeting of HLA-peptide complex using TCRL based therapies as means to overcome resistance to conventional CAR T cell therapy.
