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:Evaluation of CAR-T Cells' Cytotoxicity against Modified Solid Tumor Cell Lines.
近年来,由于技术的发展以及 CAR-T 细胞成功用于恶性 B 细胞肿瘤患者的临床治疗,过继细胞疗法获得了新的应用前景。
近年来,随着CAR-T细胞技术的发展及其成功应用于恶性B细胞肿瘤患者的临床治疗,过继细胞疗法的应用前景得到新的拓展。然而,CAR-T治疗实体瘤的疗效仍是重大的科学和临床挑战。本研究评估了第二代CAR-T细胞对经改造实体瘤细胞系的细胞毒作用。这些细胞系包括肺腺癌H522、前列腺癌PC-3M、乳腺癌MDA-MB-231和表皮样癌A431,并经慢病毒转导表达红色荧光蛋白Katushka2S和CD19抗原。结果显示,促炎细胞因子分泌增加与肿瘤细胞单层融合度下降相关。所提出的方法有望用于初步评估CAR-T细胞治疗实体瘤的疗效,并估计发生细胞因子释放综合征的风险。
In recent years, adoptive cell therapy has gained a new perspective of application due to the development of technologies and the successful clinical use of CAR-T cells for the treatment of patients with malignant B-cell neoplasms. However, the efficacy of CAR-T therapy against solid tumor remains a major scientific and clinical challenge. In this work, we evaluated the cytotoxicity of 2nd generation CAR-T cells against modified solid tumors cell lines-lung adenocarcinoma cell line H522, prostate carcinoma PC-3M, breast carcinoma MDA-MB-231, and epidermoid carcinoma A431 cell lines transduced with lentiviruses encoding red fluorescent protein Katushka2S and the CD19 antigen. A correlation was demonstrated between an increase in the secretion of proinflammatory cytokines and a decrease in the confluence of tumor cells' monolayer. The proposed approach can potentially be applied to preliminarily assess CAR-T cell efficacy for the treatment of solid tumors and estimate the risks of developing cytokine release syndrome.
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