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:Cancer/testis antigens: from serology to mRNA cancer vaccine.
癌/睾丸抗原(CTA)是一组在多种癌症组织以及睾丸和胎盘组织中表达的肿瘤抗原。
癌睾抗原(CTA)是一类肿瘤抗原,在多种癌组织以及睾丸和胎盘组织中表达。血清学和表达数据支持的 CTA 已超过 200 种。CTA 表达模式反映了配子发生与肿瘤发生过程之间的相似性。值得注意的是,CTA 在三类癌症(肺癌、膀胱癌和皮肤癌)中高表达,而这三类癌症均有金属相关病因。本文综述 CTA 的表达、调控和功能,以及其作为癌症生物标志物和治疗靶点的转化前景。许多 CTA 具有高度免疫原性和组织特异性,常在肿瘤组织中表达而在生理状态下不表达,因此有望用于癌症检测。部分 CTA 与临床结局相关,可能成为预后生物标志物。少数 CTA 定位于细胞膜,是 CAR-T 的理想靶点。越来越多证据表明,CTA 可诱导体液或细胞免疫反应,为 T 细胞受体(TCR)疗法、CAR-T、抗体治疗以及肽或 mRNA 疫苗提供癌症免疫治疗机会。事实上,CTA 是 mRNA 癌症疫苗开发中占主导地位的非突变靶点。针对 CTA 的 TCR 和疫苗临床试验显示出疗效、安全性和耐受性,但成功仅见于少数患者。仍需深入研究 CTA 的表达和功能,以改进基于 CTA 的免疫治疗。
Cancer/testis antigens (CTAs) are a group of tumor antigens expressed in numerous cancer tissues, as well as in the testis and placental tissues. There are over 200 CTAs supported by serology and expression data. The expression patterns of CTAs reflect the similarities between the processes of gametogenesis and tumorigenesis. It is notable that CTAs are highly expressed in three types of cancers (lung cancer, bladder cancer, and skin cancer), all of which have a metal etiology. Here, we review the expression, regulation, and function of CTAs and their translational prospects as cancer biomarkers and treatment targets. Many CTAs are highly immunogenic, tissue-specific, and frequently expressed in cancer tissues but not under physiological conditions, rendering them promising candidates for cancer detection. Some CTAs are associated with clinical outcomes, so they may serve as prognostic biomarkers. A small number of CTAs are membrane-bound, making them ideal targets for chimeric antigen receptor (CAR) T cells. Mounting evidence suggests that CTAs induce humoral or cellular immune responses, providing cancer immunotherapeutic opportunities for T-cell receptors (TCRs), CAR T cell, antibody-based therapy and peptide- or mRNA-based vaccines. Indeed, CTAs are the dominating non-mutated targets in mRNA cancer vaccine development. Clinical trials on CTA TCR and vaccines have shown effectiveness, safety, and tolerance, but these successes are limited to a small number of patients. In-depth studies on CTA expression and function are needed to improve CTA-based immunotherapy.
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