决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Bystander CAR(-)CD8(+) T cells in a CAR-T cell product can expand and enhance the antitumor effects of a bispecific antibody.
Bystander CAR(-)CD8(+) T cells in a CAR-T cell product can expand and enhance the antitumor effects of a bispecific antibody.
尽管双特异性抗体(BsAb)治疗是复发/难治性大B细胞淋巴瘤CAR-T细胞治疗后的一种有价值治疗选择,但为何在强化T细胞重定向治疗后仍有效,仍有待阐明。
尽管双特异性抗体(BsAb)治疗是复发/难治性大B细胞淋巴瘤患者在接受嵌合抗原受体(CAR)-T细胞治疗后的一个有价值的治疗选择,但为何在强效T细胞重定向治疗之后它仍然有效,仍有待阐明。近来,旁观者CD8+ T细胞在肿瘤免疫治疗领域的治疗潜力已受到讨论。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细胞具有增强BsAb治疗免疫应答潜力的临床意义。CAR-T细胞产品中的T细胞主要为中心记忆和效应记忆T细胞,且外周血中此类T细胞表型在CAR-T细胞治疗后显著增加。此外,针对CD8+ T细胞和CD4+ T细胞的时序性T细胞受体库分析提示,产品来源的旁观者CAR-CD8+ T细胞成功存在于复发的淋巴结中,并在BsAb治疗后于体内扩增。仍需进一步分析,但我们的发现可能有助于解释这种序贯方法的机制和获益,并强化在BsAb治疗之前先进行CAR-T细胞治疗的顺序。
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- 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.
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