CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immunotherapy for microsatellite-stable colorectal cancer: overcoming resistance and exploring novel therapeutic strategies.
Immunotherapy for microsatellite-stable colorectal cancer: overcoming resistance and exploring novel therapeutic strategies.
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微卫星稳定(MSS)结直肠癌(CRC)占所有CRC病例的85%至95%,在癌症免疫治疗时代构成了重大的治疗挑战。与对免疫检查点抑制剂表现出显著应答的微卫星高度不稳定肿瘤不同,MSS CRC由于低肿瘤突变负荷、极少的T细胞浸润以及免疫抑制性肿瘤微环境而表现出深度耐药。本文综述了MSS CRC免疫治疗试验的当前格局,包括近期报道的STELLAR-303研究,讨论了新兴的预测性生物标志物如肿瘤突变负荷、Immunoscore Immune Checkpoint(Immunoscore-IC)以及人工智能驱动的工具如Lunit SCOPE,并探索了克服免疫耐药的创新策略,包括下一代抗细胞毒性T淋巴细胞相关蛋白-4(anti-CTLA-4)抗体、程序性细胞死亡配体1(PD-L1)/白细胞介素-2(IL-2)双特异性抗体、靶向CD47的策略、疫苗以及CAR-T(CAR-T)细胞疗法。理解这些不断演变的策略对于在这一具有挑战性的患者群体中推进精准免疫治疗至关重要。
Microsatellite-stable (MSS) colorectal cancer (CRC), comprising 85% to 95% of all CRC cases, represents a significant therapeutic challenge in the era of cancer immunotherapy. Unlike microsatellite instability-high tumors that demonstrate remarkable responses to immune checkpoint inhibitors, MSS CRC exhibits profound resistance due to low tumor mutational burden, minimal T-cell infiltration, and an immunosuppressive tumor microenvironment.
This article reviews the current landscape of immunotherapy trials in MSS CRC, including the recently reported STELLAR-303 study, discusses emerging predictive biomarkers such as tumor mutational burden, Immunoscore Immune Checkpoint (Immunoscore-IC), and artificial intelligence-driven tools like Lunit SCOPE, and explores innovative strategies to overcome immune resistance, including next-generation anti-cytotoxic T-lymphocyte-associated protein-4 (anti-CTLA-4) antibodies, programmed cell death-ligand 1 (PD-L1)/interleukin-2 (IL-2) bispecific antibodies, CD47-targeting strategies, vaccines, and chimeric antigen receptor T (CAR-T) cell therapy.
Understanding these evolving strategies is critical for advancing precision immunotherapy in this challenging patient population.
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