CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immunotherapeutic Agents for Intratumoral Immunotherapy.
Immunotherapeutic Agents for Intratumoral Immunotherapy.
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使用全身免疫检查点抑制剂(ICI)和嵌合抗原受体(CAR)T细胞的免疫疗法已革新癌症治疗,但仅使部分患者获益。全身免疫疗法可引发严重自身免疫毒性和细胞因子风暴。免疫相关不良事件(irAE)及免疫抑制性肿瘤微环境(TME)均与全身免疫治疗效果不佳有关。瘤内免疫治疗可提高肿瘤内免疫治疗药物的生物利用度,从而提高疗效并减少全身毒性。临床前和临床研究显示,从小分子到异种细胞的免疫刺激性药物瘤内给药,不仅可对注射部位肿瘤产生抗肿瘤作用,也可作用于未注射病灶。本文回顾并讨论这些策略在临床前模型及临床试验中的结果,梳理瘤内免疫治疗药物的整体图景,并阐述它们如何刺激机体免疫系统、触发抗肿瘤免疫,以及临床实践中的挑战。全身与瘤内免疫治疗联合使用,可能最充分地利用机体免疫系统对抗癌症。将精准医学与癌症免疫治疗相结合,可同时靶向肿瘤中的突变靶点并改善机体免疫功能,从而最大限度发挥医疗干预效果。
Immunotherapy using systemic immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cells has revolutionized cancer treatment, but it only benefits a subset of patients. Systemic immunotherapies cause severe autoimmune toxicities and cytokine storms. Immune-related adverse events (irAEs) plus the immunosuppressive tumor microenvironment (TME) have been linked to the inefficacy of systemic immunotherapy.
Intratumoral immunotherapy that increases immunotherapeutic agent bioavailability inside tumors could enhance the efficacy of immunotherapies and reduce systemic toxicities. In preclinical and clinical studies, intratumoral administration of immunostimulatory agents from small molecules to xenogeneic cells has demonstrated antitumor effects not only on the injected tumors but also against noninjected lesions.
Herein, we review and discuss the results of these approaches in preclinical models and clinical trials to build the landscape of intratumoral immunotherapeutic agents and we describe how they stimulate the body's immune system to trigger antitumor immunity as well as the challenges in clinical practice.
Systemic and intratumoral combination immunotherapy would make the best use of the body's immune system to treat cancers. Combining precision medicine and immunotherapy in cancer treatment would treat both the mutated targets in tumors and the weakened body's immune system simultaneously, exerting maximum effects of the medical intervention.
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