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:From Bench to Bedside: Emerging Paradigms in CAR-T Cell Therapy for Solid Malignancies.
免疫治疗,尤其是CAR-T 细胞疗法,已经彻底改变了血液系统恶性肿瘤和自身免疫性疾病的治疗。
免疫治疗,尤其是 CAR-T,已革新血液系统恶性肿瘤和自身免疫性疾病的治疗。然而,由于肿瘤异质性、免疫抑制性微环境和 T 细胞浸润不足等挑战,其治疗实体瘤的疗效仍有限。本综述首先总结限制 CAR-T 治疗实体瘤的主要原因和挑战,随后概述胃癌、肝癌和胶质瘤领域最新进展,这些疾病早期试验已显示临床潜力。CRISPR 编辑及“现货型”异体 CAR-T 的进展旨在提高规模化生产能力;AI 驱动靶点发现、合成生物学和细胞因子装甲策略则旨在增强肿瘤特异性及 T 细胞持久性。此外,在临床手术及药物试验中灵活采用联合策略,例如 CAR-T 联合免疫检查点抑制剂、溶瘤病毒、CAR-NK 或 CAR 巨噬细胞,可能进一步增强抗肿瘤疗效。CAR-T 的发展凸显其重塑精准肿瘤学的潜力;通过持续基础研究、技术优化和临床完善,可为侵袭性实体瘤患者带来希望。
Immunotherapy, particularly chimeric antigen receptor T cell (CAR-T) therapy, has revolutionized the treatment of hematological malignancies and autoimmune diseases. However, its efficacy in solid tumors remains limited due to challenges such as tumor heterogeneity, an immunosuppressive microenvironment, and poor T cell infiltration. This review first summarizes the primary causes and challenges that restrict CAR-T therapy in the treatment of solid tumors, followed by an overview of recent advancements in gastric cancer, liver cancer, and glioma, where early trials have demonstrated promising clinical potential. Advances in CRISPR-edited and "off-the-shelf" allogeneic CAR-T cells seek to improve scalability, while artificial intelligence (AI)-driven target discovery, synthetic biology, and cytokine armoring strategies aim to enhance tumor specificity and T-cell persistence. Additionally, the flexible utilization of combination strategies in clinical surgical and medical trials, such as combining CAR-T therapy with immune checkpoint inhibitors, oncolytic viruses, chimeric antigen receptor NK cells (CAR-NK), or chimeric antigen receptor macrophage cells (CAR-M) may further enhance antitumor efficacy. The evolution of CAR-T therapy highlights its potential to reshape precision oncology, offering hope to patients with aggressive solid tumors through ongoing basic research, technological optimization, and clinical refinement.
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