PDF(Pubmed)
Abstract：
Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing promising results for numerous cancer patients. However, significant advancements are required before CAR-T therapies become readily available as off-the-shelf treatments, particularly for solid tumors and lymphomas. In this review, we have systematically analyzed the combination therapy involving engineered CAR-T cells and anti PD-1 agents. This approach aims at overcoming the limitations of current treatments and offers potential advantages such as enhanced tumor inhibition, alleviated T-cell exhaustion, heightened T-cell activation, and minimized toxicity. The integration of CAR-T therapy, which targets tumor-associated antigens, with PD-1 blockade augments T-cell function and mitigates immune suppression within the tumor microenvironment. To assess the impact of combination therapy on various tumors and lymphomas, we categorized them based on six major tumor-associated antigens: mesothelin, disialoganglioside GD-2, CD-19, CD-22, CD-133, and CD-30, which are present in different tumor types. We evaluated the efficacy, complete and partial responses, and progression-free survival in both pre-clinical and clinical models. Additionally, we discussed potential implications, including the feasibility of combination immunotherapies, emphasizing the importance of ongoing research to optimize treatment strategies and improve outcomes for cancer patients. Overall, we believe combining CAR-T therapy with PD-1 blockade holds promise for the next generation of cancer immunotherapy.
摘要：
目前,嵌合抗原受体T细胞（CAR-T）和免疫检查点抑制剂（如程序性细胞死亡蛋白-1（PD-1）阻断剂）等疗法对许多癌症患者显示出有希望的结果。然而,在CAR-T疗法成为现成的治疗方法之前，需要取得重大进展，特别是实体瘤和淋巴瘤。在这次审查中,我们系统分析了涉及工程化CAR-T细胞和抗PD-1药物的联合治疗.这种方法旨在克服当前治疗的局限性，并提供潜在的优势，例如增强的肿瘤抑制作用。减轻T细胞耗尽，T细胞激活增强,和最小化的毒性。CAR-T疗法的整合，靶向肿瘤相关抗原，PD-1阻断增强T细胞功能并减轻肿瘤微环境内的免疫抑制。评估联合治疗对各种肿瘤和淋巴瘤的影响，我们根据六种主要的肿瘤相关抗原对它们进行分类：间皮素，二唾液酸神经节苷脂GD-2，CD-19，CD-22，CD-133和CD-30，存在于不同的肿瘤类型。我们评估了疗效，完整和部分响应，以及临床前和临床模型中的无进展生存期。此外,我们讨论了潜在的影响，包括联合免疫疗法的可行性，强调正在进行的研究对优化癌症患者治疗策略和改善预后的重要性。总的来说,我们认为,CAR-T疗法与PD-1阻断联合应用有望成为下一代癌症免疫疗法.
