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:Immune Checkpoint Blockade and Emerging Combination Platforms in Breast Cancer: A Narrative Review.
这篇叙述性综述探讨了乳腺癌(BC)免疫治疗的最新进展,重点关注免疫检查点抑制剂(ICI)单药及与其他治疗方式的联合应用。
本叙述性综述考察乳腺癌(BC)免疫治疗的近期进展,重点关注单独使用免疫检查点抑制剂(ICI)及其与其他治疗方式的联合。KEYNOTE-522 和 IMpassion130 等里程碑试验已确立 pembrolizumab 和 atezolizumab 在三阴性乳腺癌(TNBC)中的疗效。然而,乳腺癌仍是癌症相关死亡的主要原因之一,凸显开发新疗法的必要性。本文将联合策略归纳为三类机制:一是重塑免疫抑制性肿瘤微环境(化疗、PARP 抑制剂、溶瘤病毒);二是增强效应细胞持续性(CAR-T、CAR-NK、细胞因子支持);三是调节 PD-1/CTLA-4 之外的免疫检查点轴(LAG-3、TIM-3、TIGIT)。已有研究显示,ICI 与 CAR-T 细胞、CAR-NK 细胞、溶瘤病毒及外泌体联用可改善抗肿瘤免疫应答。本综述为基于生物标志物的患者分层提供转化框架,并审慎评估新兴平台的临床成熟度。仍需更多研究和临床试验,以扩大这些策略在不同乳腺癌亚型中的适用性并改善患者结局。
This narrative review examines recent progress in immunotherapy for breast cancer (BC), focusing on immune checkpoint inhibitors (ICIs) alone and in combination with other modalities. Landmark trials such as KEYNOTE-522 and IMpassion130 have established the efficacy of pembrolizumab and atezolizumab in triple-negative breast cancer (TNBC). However, BC remains a leading cause of cancer-related fatalities, underscoring the need for novel approaches. We synthesize combination strategies into three mechanistic categories: (I) those that remodel the immunosuppressive tumor microenvironment (chemotherapy, PARP inhibitors, oncolytic viruses); (II) those that enhance effector cell persistence (CAR-T, CAR-NK, cytokine support); and (III) those that modulate immune checkpoint axes beyond PD-1/CTLA-4 (LAG-3, TIM-3, TIGIT). Combining ICIs with CAR-T cells, CAR-NK cells, oncolytic viruses, and exosomes has been shown to improve antitumor immune responses. This review provides a translational framework for biomarker-driven patient stratification and critically evaluates the clinical maturity of emerging platforms. Further research and clinical trials are needed to expand applicability across BC subtypes and improve patient outcomes.
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