T-cell redirection therapy using chimeric antigen receptor (CAR) T cells and/or bispecific antibody (BsAb) has been established and become a promising treatment strategy for relapsed/refractory B-cell lymphomas. To further improve their therapeutic efficacy, assessment of their in vivo mechanisms and the ways of sequential approaches are necessary.
In this study, we have chronologically analyzed T-cell clones and their memory phenotypes in peripheral blood mononuclear cells (PBMCs) and lymph node cells collected at the different time points through a lymphoma case treated with CD20 x CD3 BsAb following CD19 CAR-T cell therapy. First, memory-formed T cells had successfully expanded in peripheral blood and lymph node after CAR-T cell therapy when compared with those at the timing of apheresis. Those memory T-cell population had increased more after BsAb therapy. Then, we had labelled both CD3⁺CD8⁺ T cells and CD3⁺CD4⁺ T cells collected from the apheresis product using TCR-β gene, and followed their T-cell clones. Interestingly, product-derived bystander CAR-negative CD8⁺ T cells had expanded after CAR-T cell therapy, infiltrated in relapsed lymph node, and further propagated after BsAb therapy, which resulted in complete remission of tumors.
Therefore, these findings might support a new therapeutic effect of bystander CAR^-CD8⁺ T cells in a CAR-T cell product in combination with BsAb, and strengthen such sequential approaches using CAR-T and BsAb therapy.