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:Focusing on Prostate-Specific Membrane Antigen in Precision Diagnosis and Treatment of Prostate Cancer.
本综述总结的证据强调 PSMA 作为关键分子靶点,支持前列腺癌治疗的整个过程中的精确诊断和个性化治疗。
前列腺癌(PCa)是男性泌尿生殖系统最常见的恶性肿瘤,近年来其发病率和死亡率在全球范围内呈显著上升趋势。前列腺特异性膜抗原(PSMA)是一种在PCa细胞中高表达的II型跨膜糖蛋白,已成为PCa精准诊断与治疗领域的重要分子靶点。近年来,基于PSMA的分子影像、放射性配体治疗及新型靶向药物研发均取得了显著进展。本文旨在总结并批判性探讨PSMA靶向分子影像、放射性配体治疗及新兴治疗策略的最新进展,重点阐述其在PCa精准诊断和个体化治疗中的作用。使用68 Ga和18 F等放射性核素的PSMA正电子发射断层扫描/计算机断层扫描(PET/CT)显像显著提高了原发肿瘤分期、复发病灶定位及治疗反应评估的准确性。放射性配体治疗,如177 Lu-PSMA-617和225 Ac-PSMA-617,在多项临床试验中延长了生存期并显示出症状获益,目前已被应用于早期疾病阶段,包括未接受化疗和激素敏感阶段。与此同时,PSMA靶向抗体及抗体药物偶联物(PSMA-ADC),以及双特异性T细胞衔接器(BiTE)和CAR-T 细胞疗法正在不断优化,展现出良好的临床潜力。此外,PSMA靶向纳米平台能够精确递送化疗药物、光敏剂或影像探针,实现多模态影像引导下的一体化诊断和治疗,为个体化治疗提供新策略。总而言之,本综述总结的证据强调 PSMA 作为关键分子靶点,支持前列腺癌治疗的整个过程中的精确诊断和个性化治疗。
Prostate cancer (PCa) is the most common malignant tumor of the male genitourinary system, and its incidence and mortality have shown a marked global increase in recent years. Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein highly expressed in PCa cells, has emerged as a vital molecular target in the field of PCa precision diagnosis and therapy. In recent years, significant advances have been achieved in PSMA-based molecular imaging, radioligand therapy, and the development of novel targeted drugs. This review aims to summarize and critically discuss recent advances in PSMA-targeted molecular imaging, radioligand therapy, and emerging therapeutic strategies, highlighting their roles in precision diagnosis and personalized treatment of PCa. PSMA positron emission tomography/computed tomography (PET/CT) imaging using radionuclides such as 68 Ga and 18 F has markedly improved the accuracy of primary tumor staging, localization of recurrent lesions, and therapeutic response assessment. Radioligand therapies, such as 177 Lu-PSMA-617 and 225 Ac-PSMA-617, have prolonged survival and demonstrated symptomatic benefits in multiple clinical trials, and are now applied in early disease stages, including chemotherapy-na ve and hormone-sensitive settings. Meanwhile, PSMA-targeted antibodies and antibody-drug conjugates (PSMA-ADCs), as well as bispecific T-cell engagers (BiTEs) and chimeric antigen receptor T-cell (CAR-T) therapies, are constantly being optimized and show promising clinical potential. Furthermore, PSMA-targeted nanoplatforms enable precise delivery of chemotherapeutic agents, photosensitizers, or imaging probes, achieving integrated diagnosis and therapy with multimodal imaging guidance, and offering new strategies for individualized treatment. Taken together, the evidence summarized in this review highlights PSMA as a pivotal molecular target supporting precision diagnosis and personalized treatment across the continuum of prostate cancer management.
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