Kato Junichi, Konishi Tatsuya, Honda Takatsugu, Maruta Masaki, Nabe Shogo, Masuda Yuya, Matsumoto Meika, Kawasaki Natsumi, Miyazaki Yukihiro, Doi Yasukazu, Takasuka Yasunori, Yamanouchi Jun, Ochi Toshiki, Takenaka Katsuto
Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Division of Blood Transfusion and Cell Therapy, Ehime University Hospital, Toon, Ehime, Japan.
J Immunother Cancer. 2025 Jun 24;13(6):e011690. doi: 10.1136/jitc-2025-011690.
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 CARCD8 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.
尽管双特异性抗体(BsAb)治疗是嵌合抗原受体(CAR)-T细胞疗法治疗复发/难治性大B细胞淋巴瘤后的一种有价值的治疗选择,但在强化T细胞重定向治疗后其仍有效的原因尚待阐明。最近,癌症免疫治疗领域中旁观者CD8 T细胞的治疗潜力已被讨论。在本研究中,我们通过一例CD19 CAR-T细胞治疗后复发的弥漫性大B细胞淋巴瘤病例,展示了CAR-T细胞产品中旁观者CAR阴性CD8 T细胞有可能通过增强BsAb治疗的免疫反应而产生临床影响。CAR-T细胞产品中的T细胞主要表现为中枢和效应记忆T细胞,且CAR-T细胞治疗后外周血中此类T细胞表型显著增加。此外,对CD8 T细胞和CD4 T细胞进行的时间顺序T细胞受体-β谱系分析表明,产品来源的旁观者CAR CD8 T细胞在复发淋巴结中成功存在,并在BsAb治疗后在体内扩增。虽然还需要进一步分析,但我们的发现可能有助于解释这种序贯治疗方法的机制和益处,并加强CAR-T细胞治疗先于BsAb治疗的顺序。
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