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免疫检查点与 CAR-T 细胞:未来癌症疗法的先驱?

Immune Checkpoints and CAR-T Cells: The Pioneers in Future Cancer Therapies?

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran.

Student Research Committee, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran.

出版信息

Int J Mol Sci. 2020 Nov 5;21(21):8305. doi: 10.3390/ijms21218305.


DOI:10.3390/ijms21218305
PMID:33167514
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7663909/
Abstract

Although the ever-increasing number of cancer patients pose substantial challenges worldwide, finding a treatment with the highest response rate and the lowest number of side effects is still undergoing research. Compared to chemotherapy, the relatively low side effects of cancer immunotherapy have provided ample opportunity for immunotherapy to become a promising approach for patients with malignancy. However, the clinical translation of immune-based therapies requires robust anti-tumoral immune responses. Immune checkpoints have substantial roles in the induction of an immunosuppressive tumor microenvironment and tolerance against tumor antigens. Identifying and targeting these inhibitory axes, which can be established between tumor cells and tumor-infiltrating lymphocytes, can facilitate the development of anti-tumoral immune responses. Bispecific T-cell engagers, which can attract lymphocytes to the tumor microenvironment, have also paved the road for immunological-based tumor elimination. The development of CAR-T cells and their gene editing have brought ample opportunity to recognize tumor antigens, independent from immune checkpoints and the major histocompatibility complex (MHC). Indeed, there have been remarkable advances in developing various CAR-T cells to target tumoral cells. Knockout of immune checkpoints via gene editing in CAR-T cells might be designated for a breakthrough for patients with malignancy. In the midst of this fast progress in cancer immunotherapies, there is a need to provide up-to-date information regarding immune checkpoints, bispecific T-cell engagers, and CAR-T cells. Therefore, this review aims to provide recent findings of immune checkpoints, bispecific T-cell engagers, and CAR-T cells in cancer immunotherapy and discuss the pertained clinical trials.

摘要

尽管癌症患者的数量不断增加,给全球带来了巨大的挑战,但寻找一种具有最高反应率和最低副作用的治疗方法仍在研究中。与化疗相比,癌症免疫疗法的副作用相对较低,为免疫疗法为恶性肿瘤患者提供了一个有前途的治疗方法提供了充足的机会。然而,免疫疗法的临床转化需要强大的抗肿瘤免疫反应。免疫检查点在诱导免疫抑制性肿瘤微环境和对肿瘤抗原的耐受性方面起着重要作用。鉴定和靶向这些抑制性轴,这些抑制性轴可以在肿瘤细胞和肿瘤浸润淋巴细胞之间建立,可以促进抗肿瘤免疫反应的发展。双特异性 T 细胞衔接器可以吸引淋巴细胞进入肿瘤微环境,也为免疫为基础的肿瘤消除铺平了道路。嵌合抗原受体 T 细胞(CAR-T 细胞)的发展及其基因编辑为识别肿瘤抗原带来了机会,而无需依赖免疫检查点和主要组织相容性复合体(MHC)。事实上,已经有了开发各种针对肿瘤细胞的 CAR-T 细胞的显著进展。通过基因编辑在 CAR-T 细胞中敲除免疫检查点可能是恶性肿瘤患者的一个突破。在癌症免疫疗法快速发展的过程中,有必要提供有关免疫检查点、双特异性 T 细胞衔接器和 CAR-T 细胞的最新信息。因此,本综述旨在提供有关免疫检查点、双特异性 T 细胞衔接器和 CAR-T 细胞在癌症免疫治疗中的最新发现,并讨论相关的临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb7/7663909/2975fca7655c/ijms-21-08305-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb7/7663909/b61fa77bd0f1/ijms-21-08305-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb7/7663909/d7b7483567bb/ijms-21-08305-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb7/7663909/2975fca7655c/ijms-21-08305-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb7/7663909/b61fa77bd0f1/ijms-21-08305-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb7/7663909/d7b7483567bb/ijms-21-08305-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb7/7663909/2975fca7655c/ijms-21-08305-g003.jpg

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本文引用的文献

[1]
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