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:IL-27-engineered CAR.19-NK-92 cells exhibit enhanced therapeutic efficacy.
IL-27-engineered CAR.19-NK-92 cells exhibit enhanced therapeutic efficacy.
自然杀伤(NK)细胞的嵌合抗原受体(CAR)工程化在早期临床研究中显示出有前景的结果。
CAR-NK细胞在早期临床研究中显示良好前景,但仍需进一步提高疗效。本研究考察在NK-92细胞中表达IL-27的第四代CD19 CAR。IL-27显著增强NK-92细胞对B细胞肿瘤细胞系的增殖和细胞毒作用,在体外及小鼠淋巴瘤异种移植模型中均有效。对活化CAR变体的系统转录组分析进一步支持IL-27可为第四代CAR提供关键生长和活化信号,克服NK细胞靶向治疗的局限。将IL-27整合进CAR-NK是增强治疗潜力、诱发强抗癌反应的有前景策略,为第四代CAR工程和NK细胞免疫疗法提供了证据。
Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells has shown promising results in early-phase clinical studies. However, advancing CAR-NK cell therapeutic efficacy is imperative. In this study, we investigated the impact of a fourth-generation CD19-targeted CAR (CAR.19) coexpressing IL-27 on NK-92 cells. We observed a significant improvement in NK-92 cell proliferation and cytotoxicity activity against B-cell cancer cell lines, both in vitro and in a xenograft mouse B-cell lymphoma model. Our systematic transcriptome analysis of the activated NK-92 CAR variants further supports the potential of IL-27 in fourth-generation CARs to overcome limitations of NK cell-based targeted tumor therapies by providing essential growth and activation signals. Integrating IL-27 into CAR-NK cells emerges as a promising strategy to enhance their therapeutic potential and elicit robust responses against cancer cells. These findings contribute substantially to the mounting evidence supporting the potential of fourth-generation CAR engineering in advancing NK cell-based immunotherapies.
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