image: A CAR-T cell product can contain both CAR-T cells and CAR-negative bystander T cells (left). After treatment with CAR-T cell therapy, CAR-T cells kill tumor cells and release a panel of cytokines. In the presence of those cytokines, simultaneously transferred product-derived bystander T cells and remaining bystander T cells in the body have an opportunity to expand and form memory T cells (middle). Especially, product-derived bystander CAR-CD8+ T cells can further proliferate after BsAb therapy, resulting in enhanced therapeutic effects against relapsed tumor cells (right).
Credit: Junichi Kato,Tatsuya Konishi,Toshiki Ochi,Katsuto Takenaka,Ehime university
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.
Journal
Journal for ImmunoTherapy of Cancer