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工程化 CAR-T 细胞与 PD-1 阻断联合免疫治疗在淋巴瘤和实体瘤中的协同作用:系统评价。

The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review.

机构信息

Department of Zoology, Non-Coding RNA and Cancer Biology Laboratory, Central University of Punjab, Bathinda, Punjab, India.

Department of Biochemistry, School of Basic Sciences, Central University of Punjab, Bathinda, Punjab, India.

出版信息

Front Immunol. 2024 May 10;15:1389971. doi: 10.3389/fimmu.2024.1389971. eCollection 2024.


DOI:10.3389/fimmu.2024.1389971
PMID:38799440
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11116574/
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)疗法和程序性细胞死亡蛋白 1(PD-1)抑制剂等免疫检查点抑制剂在众多癌症患者中显示出了有前景的结果。然而,在 CAR-T 疗法成为现成的治疗方法之前,还需要取得重大进展,特别是对于实体瘤和淋巴瘤。在这篇综述中,我们系统地分析了涉及工程 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方法的局限性,并提供潜在的优势,如增强肿瘤抑制、减轻 T 细胞衰竭、提高 T 细胞激活和最小化毒性。靶向肿瘤相关抗原的 CAR-T 疗法与 PD-1 阻断的结合增强了 T 细胞功能,并减轻了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,我们根据六种主要的肿瘤相关抗原对它们进行了分类:间皮素、二唾液酸神经节苷脂 GD-2、CD-19、CD-22、CD-133 和 CD-30,它们存在于不同的肿瘤类型中。我们评估了临床前和临床模型中的疗效、完全和部分缓解以及无进展生存期。此外,我们讨论了潜在的意义,包括联合免疫疗法的可行性,强调了正在进行的研究的重要性,以优化治疗策略并改善癌症患者的结局。总的来说,我们相信将 CAR-T 疗法与 PD-1 阻断联合使用为下一代癌症免疫疗法带来了希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c81a/11116574/13632f630e13/fimmu-15-1389971-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c81a/11116574/2f34b1f00c3e/fimmu-15-1389971-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c81a/11116574/3ea0f1300d21/fimmu-15-1389971-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c81a/11116574/685660da415a/fimmu-15-1389971-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c81a/11116574/13632f630e13/fimmu-15-1389971-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c81a/11116574/2f34b1f00c3e/fimmu-15-1389971-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c81a/11116574/3ea0f1300d21/fimmu-15-1389971-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c81a/11116574/685660da415a/fimmu-15-1389971-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c81a/11116574/13632f630e13/fimmu-15-1389971-g004.jpg

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[6]
Selective JAK2 pathway inhibition enhances anti-leukemic functionality in CD19 CAR-T cells.

Cancer Immunol Immunother. 2025-2-1

[7]
Identification of Transcriptional Regulators of Immune Evasion Across Cancers: An Alternative Immunotherapeutic Strategy for Cholangiocarcinoma.

Cancers (Basel). 2024-12-17

本文引用的文献

[1]
FDA approves first tumour-infiltrating lymphocyte (TIL) therapy, bolstering hopes for cell therapies in solid cancers.

Nat Rev Drug Discov. 2024-4

[2]
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Ther Adv Med Oncol. 2023-11-10

[3]
Targeted delivery of a PD-1-blocking scFv by CD133-specific CAR-T cells using nonviral Sleeping Beauty transposition shows enhanced antitumour efficacy for advanced hepatocellular carcinoma.

BMC Med. 2023-8-28

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Long-term Complete Remission of Decitabine-Primed Tandem CD19/CD22 CAR-T Therapy with PD-1 and BTK Inhibitors Maintenance in a Refractory Primary Central Nervous System Lymphoma Patient.

Cancer Res Treat. 2023-10

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Front Immunol. 2023

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Int J Mol Sci. 2023-5-13

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Br J Haematol. 2023-7

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Int J Mol Sci. 2023-2-20

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[10]
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J Immunother Cancer. 2023-1

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