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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Possible Role of Immunotherapy in Locally Advanced Pancreatic Cancer Treatment.
The Possible Role of Immunotherapy in Locally Advanced Pancreatic Cancer Treatment.
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LAPC 仍是最致命的恶性肿瘤之一,免疫治疗提供了潜在可能,但受限于生存获益有限和不良反应。聚焦新型药物、优化联合方案以及克服肿瘤耐药机制的进一步研究,对于改善这一棘手疾病的结局至关重要。
局部晚期胰腺癌 (LAPC) 是胰腺癌的一个重要亚型,其特点是预后不良和治疗选择有限。包括放化疗在内的传统疗法的成功有限,这引发了人们对免疫疗法等创新策略的兴趣。本综述评估了免疫疗法在 LAPC 中的作用。
对于本次综述,我们于 2024 年 8 月对 PubMed 数据库进行了全面检索。应用排除标准后,分析中纳入了 26 项研究。
免疫检查点抑制剂产生了不一致的临床结果,无进展生存期略有改善,但副作用显着。癌症疫苗,特别是组合方案中的 GVAX,已在临床前和临床环境中展现出潜力,成纤维细胞激活蛋白 (FAP) 和 mKRAS 特异性两亲疫苗也同样如此。针对各种抗原的嵌合抗原受体 (CAR) T 细胞疗法已经取得了令人鼓舞的结果,但面临着安全性和有效性的挑战。新兴方法,包括 Toll 样受体激动剂、肿瘤相关巨噬细胞靶向和放射免疫疗法,也显示出临床前前景,但需要进一步研究。尽管进行了大量研究,免疫疗法对 LAPC 的总体影响仍然有限。一些涉及检查点抑制剂、疫苗和 CAR-T 细胞的联合疗法已显示出积极的结果;然而,许多都受到免疫抑制环境和肿瘤毒性的阻碍。最近的研究强调需要进一步研究来完善这些策略并改善治疗选择。
Locally advanced pancreatic cancer (LAPC) represents a significant subset of pancreatic cancers and is characterized by a poor prognosis and limited treatment options. Conventional therapies, including chemoradiotherapy, have demonstrated limited success, prompting interest in innovative strategies, such as immunotherapy. This review evaluates the role of immunotherapy in LAPC.
For this review, a comprehensive search of the PubMed database was conducted in August 2024. After applying the exclusion criteria, 26 studies were included in the analysis.
Immune checkpoint inhibitors have produced inconsistent clinical outcomes, with modest improvements in progression-free survival and significant side effects. Cancer vaccines, particularly GVAX in combination regimens, have demonstrated potential, as have fibroblast activation protein (FAP) and mKRAS-specific amphiphile vaccines in preclinical and clinical settings. Chimeric antigen receptor (CAR) T-cell therapies targeting various antigens have yielded encouraging outcomes but have faced safety and efficacy challenges. Emerging approaches, including Toll-like receptor agonists, tumor-associated macrophage targeting, and radioimmunotherapy, have also shown preclinical promise but require further study. Despite numerous investigations, the overall impact of immunotherapy on LAPC remains limited. Some combination therapies involving checkpoint inhibitors, vaccines, and CAR T cells have shown positive outcomes; however, many are hindered by the immunosuppressive environment and toxicity of tumors. Recent studies emphasize the need for further research to refine these strategies and improve treatment options.
LAPC remains one of the deadliest malignancies, with immunotherapy offering potential but constrained by limited survival benefits and adverse effects. Further studies focusing on novel agents, refined combinations, and overcoming tumor resistance mechanisms are critical to improve outcomes for this challenging disease.
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