肿瘤细胞治疗研究
英文原题：Novel Immunotherapeutic Strategies for Castration-Resistant Prostate Cancer: Mechanisms and Clinical Advances.
在双特异性抗体（如 Xaluritamig 达到 59% PSA50 缓解）、PSMA-CAR-T（P-PSMA-101）和溶瘤病毒（Ad5 PSA/MUC-1/brachyury）等新方法中观察到了初步疗效。
前列腺癌常进展为致死性、耐药的去势抵抗性前列腺癌（CRPC），此时传统疗法往往因内在和获得性耐药机制而失败。这种耐药性造成了关键的治疗僵局，使患者选择有限且预后不良。免疫疗法已成为一种有前景的策略，利用免疫系统对抗这些难治性肿瘤，为克服CRPC耐药背后的免疫抑制屏障提供了潜在途径。本综述综合了PubMed、Web of Science和Embase（2020-2025）结构化检索的结果，揭示了显著的临床进展：已开展4项疫苗试验、5项免疫检查点抑制剂试验、18项联合治疗试验（≥2种药物）和6项靶向药物试验。在双特异性抗体（如Xaluritamig达到59% PSA50缓解）、PSMA-CAR-T（P-PSMA-101）和溶瘤病毒（Ad5 PSA/MUC-1/brachyury）等新方法中观察到了初步疗效。基础研究确定了四种靶向耐药机制（如AR-LLT1、Pygo2和HnRNP L）以及一种纳米颗粒介导的三联疗法（CM-AMS@AD NPs整合光热、化疗和免疫治疗），该疗法在临床前增强了细胞毒性T细胞浸润并抑制了CRPC生长。这些综合发现表明免疫疗法在克服CRPC耐药屏障和改善患者预后方面具有潜力，其中双特异性T细胞衔接器（Xaluritamig，59% PSA50）和PSMA导向的CAR-T疗法（P-PSMA-101，>50% PSA下降）成为最有前景的近期候选方案，以及生物标志物分层的联合方案（nivolumab联合rucaparib，84.6% PSA50，在HRR缺陷患者中）说明了精准患者选择的变革性力量；然而，这些发现需要在更大规模、生物标志物分层的试验中验证，才能得出明确结论。要将这一潜力转化为临床现实，需要通过预测性生物标志物优化患者选择，并开展严格验证的III期试验，以确认持久的临床缓解和长期生存获益。
Prostate cancer frequently progresses to lethal, drug-resistant castration-resistant prostate cancer (CRPC), where conventional therapies often fail due to intrinsic and acquired resistance mechanisms. This resistance creates a critical therapeutic impasse, leaving patients with limited options and poor prognoses. Immunotherapy has emerged as a promising strategy to harness the immune system against these treatment-refractory tumors, offering a potential avenue to overcome the immunosuppressive barriers that underlie CRPC drug resistance. This review synthesizes findings from a structured search of PubMed, Web of Science, and Embase (2020-2025), revealing significant clinical progress: 4 vaccine trials, 5 immune checkpoint inhibitor trials, 18 combination therapy trials ( 2 agents), and 6 targeted drug trials have been conducted. Preliminary efficacy was observed in novel approaches like bispecific antibodies (e.g., Xaluritamig achieving 59% PSA50 response), PSMA-CAR-T (P-PSMA-101), and oncolytic viruses (Ad5 PSA/MUC-1/brachyury). Basic research identified four targeted resistance mechanisms (e.g., AR-LLT1, Pygo2, and HnRNP L) and one nanoparticle-mediated triple-combination therapy (CM-AMS@AD NPs integrating photothermal, chemotherapy, and immunotherapy), which enhanced cytotoxic T-cell infiltration and suppressed CRPC growth preclinically. These collective findings suggest the potential of immunotherapy for CRPC in overcoming resistance barriers and improving patient outcomes, with bispecific T cell engagers (Xaluritamig, 59% PSA50) and PSMA-directed CAR-T therapy (P-PSMA-101, >50% PSA reduction) emerging as the most promising near-term candidates and biomarker-stratified combinations (nivolumab plus rucaparib, 84.6% PSA50, in HRR-deficient patients) illustrating the transformative power of precision patient selection; however, these findings require validation in larger, biomarker-stratified trials before definitive conclusions can be drawn. Translating this potential into clinical reality requires optimized patient selection through predictive biomarkers and rigorously validated Phase III trials to confirm durable clinical responses and long-term survival benefits.
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