Bystander CAR-CD8+ T cells in a CAR-T cell product can expand and enhance the antitumor effects of a bispecific antibody.

Abstract

Although bispecific antibody (BsAb) treatment is a valuable therapeutic option for post chimeric antigen receptor (CAR)-T cell therapy against relapsed/refractory large B-cell lymphoma, it remains to be clarified why it is still effective after intensive T-cell redirection therapy. Recently, the therapeutic potential of bystander CD8⁺ T cells in the field of cancer immunotherapy have been discussed. In this study, we have shown a clinical impact where bystander CAR-negative CD8⁺ T cells from a CAR-T cell product have a potential to augment immune responses of BsAb therapy through a case with relapsed diffuse large B-cell lymphoma after CD19 CAR-T cell therapy. T cells in a CAR-T-cell product dominantly showed central and effector memory T cells, and such T-cell phenotypes in peripheral blood significantly increased after CAR-T cell therapy. Furthermore, chronological T-cell receptor-β repertoire analyses for both CD8⁺ T cells and CD4⁺ T cells suggested that product-derived bystander CAR^-CD8⁺ T cells successfully existed in a relapsed lymph node and expanded in the body after BsAb therapy. Further analyses are necessary, but our findings might help to explain the mechanisms and benefits of this sequential approach and strengthen the sequence of CAR-T cell therapy prior to BsAb therapy.