Discovery of new therapeutic effects induced by CAR-T cell therapy

We have proposed a new therapeutic effect of CAR-T-cell therapy through a lymphoma case treated with bispecific antibody（BsAb）. Memory-formed T cells had been developed in the body after CAR-T-cell therapy. Interestingly, bystander CAR-negative CD8⁺ T cells in the CAR-T-cell product successfully expanded in periphery and lymph node, and mostly propagated after treatment with BsAb, which resulted in complete remission. Therefore, such sequential approach using CAR-T/BsAb might have a potential to further enhance antitumor effects.

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.

Reference URL: https://jitc.bmj.com/content/13/6/e011690

Bibliographic Information

Bystander CAR^-CD8⁺ T cells in a CAR-T cell product can expand and enhance the antitumor effects of a bispecific antibody.
Junichi Kato, Tatsuya Konishi, Takatsugu Honda, Masaki Maruta, Shogo Nabe, Yuya Masuda, Meika Matsumoto, Natsumi Kawasaki, Yukihiro Miyazaki, Yasukazu Doi, Yasunori Takasuka, Jun Yamanouchi, Toshiki Ochi, Katsuto Takenaka
J Immunother Cancer, 13（6）, e011690,
doi: 10.1136/jitc-2025-011690, 2025（June 24）.

Fundings

• Daiichi Sankyo Co.

Fundings

• Otsuka Pharmaceutical

Media

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  The roles of CAR-T product-derived bystander T cells for BsAb therapy.

  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
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