决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review.
目前,诸如CAR-T 细胞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,正在为众多癌症患者展现出令人鼓舞的结果。
目前,诸如CAR-T 细胞和免疫检查点抑制剂如程序性细胞死亡蛋白-1(PD-1)阻断剂等疗法在众多癌症患者中显示出令人鼓舞的结果。然而,在CAR-T疗法成为现成可用的治疗选择之前,仍需取得重大进展,尤其是针对实体瘤和淋巴瘤。在本综述中,我们系统分析了涉及工程化CAR-T细胞与抗PD-1药物的联合治疗。该方法旨在克服当前治疗的局限性,并提供潜在优势,如增强肿瘤抑制、缓解T细胞耗竭、提高T细胞活化以及降低毒性。将靶向肿瘤相关抗原的CAR-T疗法与PD-1阻断相结合,可增强T细胞功能并减轻肿瘤微环境中的免疫抑制。为了评估联合治疗对各种肿瘤和淋巴瘤的影响,我们根据六种主要肿瘤相关抗原对其进行分类:间皮素、双唾液酸神经节苷脂GD-2、CD-19、CD-22、CD-133和CD-30,这些抗原存在于不同肿瘤类型中。我们评估了临床前和临床模型中的疗效、完全缓解和部分缓解以及无进展生存期。此外,我们讨论了潜在意义,包括联合免疫疗法的可行性,强调持续研究以优化治疗策略和改善癌症患者预后的重要性。总体而言,我们认为将CAR-T疗法与PD-1阻断相结合有望成为下一代癌症免疫治疗。
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.
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