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:Two Are Better than One: The Bi-Specific Antibody Mosunetuzumab Reveals an Improved Immune Response of Vγ9Vδ2 T Cells Targeting CD20 in Malignant B Cells in Comparison to the Mono-Specific Antibody Obinutuzumab.
我们认为刺激后的γδ T细胞与mosunetuzumab联合是一种有前景的治疗方法,值得未来开展临床试验。
在癌症治疗中,免疫治疗已被确立为临床实践中的后线治疗选择。这包括干细胞移植、修饰或激活的免疫细胞,以及针对异常细胞的抗体。作为一种非常规免疫细胞亚群,γδ T细胞已被证明可对恶性细胞产生作用。它们表现出不依赖MHC的激活过程,这可在过继转移同种异体细胞后减轻移植物抗宿主病。在过去几年中,治疗性抗体的疗效已得到改善。作为一种双特异性抗体,mosunetuzumab同时结合CD3和CD20,从而使效应细胞与靶细胞紧密接近。在此,我们着手分析γδ T细胞与mosunetuzumab联合应用相较于单克隆抗CD20抗体obinutuzumab的抗肿瘤效应效率。mosunetuzumab使γδ T细胞在IFN-γ和CD107a表达以及对来自淋巴瘤B细胞系的恶性B细胞的细胞毒性方面表现出改善的应答。与obinutuzumab相比,mosunetuzumab对B细胞淋巴瘤细胞系和原发患者样本产生了相当或增强的细胞毒性,其中这一效应更为突出。总之,我们认为刺激后的γδ T细胞与mosunetuzumab联合是一种有望用于未来临床试验的治疗方法。
In treating cancer, immunotherapy has been established as a later-line treatment option in clinical practice. That includes stem cell transplantation, modified or activated immune cells, and antibodies directed against aberrant cells. As an unconventional immune cell subgroup, γδ T cells have been shown to provide effects against malignant cells. They exhibit an MHC-independent activation process, which could diminish graft-versus-host disease after an adoptive transfer of allogeneic cells. Over the last years, the efficacy of therapeutic antibodies has been improved. As a bi-specific antibody, mosunetuzumab binds to both CD3 and CD20, thereby providing close proximity between effector and target cells. Here, we set out to analyze the efficiency of γδ T cells' anti-tumor effects in combination with mosunetuzumab vs. the monoclonal anti-CD20 antibody obinutuzumab. Mosunetuzumab revealed improved responses of γδ T cells regarding their expression of IFN-γ and CD107a and their cytotoxicity towards malignant B cells from lymphoma B cell lines. In comparison to obinutuzumab, mosunetuzumab led to an equivalent or enhanced cytotoxicity against B cell lymphoma cell lines and primary patient samples, where this effect was even more prominent. In summary, we consider the combination of stimulated γδ T cells and mosunetuzumab to be a promising therapeutic approach for future clinical trials.
MEMBER ACCOUNT
登录成功会直接打开下一页。