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嵌合抗原受体T细胞疗法治疗黑色素瘤。

Chimeric antigen receptor T-cell therapy for melanoma.

作者信息

Razavi Azadehsadat, Keshavarz-Fathi Mahsa, Pawelek John, Rezaei Nima

机构信息

Department of Animal Biology, Faculty of Biology Sciences, University of Kharazmi, Tehran, Iran.

Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.

出版信息

Expert Rev Clin Immunol. 2021 Mar;17(3):209-223. doi: 10.1080/1744666X.2021.1880895. Epub 2021 Jan 31.

DOI:10.1080/1744666X.2021.1880895
PMID:33481629
Abstract

INTRODUCTION

In recent years, chimeric antigen receptor (CAR) T cell therapy has emerged as a cancer treatment. After initial therapeutic success for hematologic malignancies, this approach has been extended for the treatment of solid tumors including melanoma.

AREAS COVERED

T cells need to be reprogramed to recognize specific antigens expressed only in tumor cells, a difficult problem since cancer cells are simply transformed normal cells. Tumor antigens, namely, CSPG4, CD70, and GD2 have been targeted by CAR-T cells for melanoma. Moreover, different co-stimulatory signaling domains need to be selected to direct T cell fate. In this review, various approaches for the treatment of melanoma and their effectiveness are comprehensively reviewed and the current status, challenges, and future perspective of CAR-T cell therapy for melanoma are discussed. Literature search was accomplished in three databases (PubMed, Google scholar, and Clinicaltrials.gov). Published papers and clinical trials were screened and relevant documents were included by checking pre-defined eligibility criteria.

EXPERT OPINION

Despite obstacles and the risk of adverse events, CAR T cell therapy could be used for patients with treatment-resistant cancer. Clinical trials are underway to determine the efficacy of this approach for the treatment of melanoma.

摘要

引言

近年来,嵌合抗原受体(CAR)T细胞疗法已成为一种癌症治疗方法。在血液系统恶性肿瘤取得初步治疗成功后,这种方法已扩展至包括黑色素瘤在内的实体瘤治疗。

涵盖领域

T细胞需要重新编程以识别仅在肿瘤细胞中表达的特定抗原,这是一个难题,因为癌细胞只是转化的正常细胞。肿瘤抗原,即硫酸软骨素蛋白聚糖4(CSPG4)、CD70和GD2已成为CAR-T细胞治疗黑色素瘤的靶点。此外,需要选择不同的共刺激信号域来引导T细胞命运。在本综述中,全面回顾了治疗黑色素瘤的各种方法及其有效性,并讨论了CAR-T细胞治疗黑色素瘤的现状、挑战和未来前景。在三个数据库(PubMed、谷歌学术和Clinicaltrials.gov)中进行了文献检索。通过检查预定义的纳入标准,筛选已发表的论文和临床试验,并纳入相关文献。

专家意见

尽管存在障碍和不良事件风险,但CAR T细胞疗法可用于治疗难治性癌症患者。目前正在进行临床试验以确定这种方法治疗黑色素瘤的疗效。

相似文献

1
Chimeric antigen receptor T-cell therapy for melanoma.嵌合抗原受体T细胞疗法治疗黑色素瘤。
Expert Rev Clin Immunol. 2021 Mar;17(3):209-223. doi: 10.1080/1744666X.2021.1880895. Epub 2021 Jan 31.
2
Chimeric antigen receptor-engineered T-cell therapy for liver cancer.嵌合抗原受体修饰的 T 细胞治疗肝癌。
Hepatobiliary Pancreat Dis Int. 2018 Aug;17(4):301-309. doi: 10.1016/j.hbpd.2018.05.005. Epub 2018 May 24.
3
CAR-T cell therapy in melanoma: A future success story?嵌合抗原受体 T 细胞疗法治疗黑色素瘤:未来的成功故事?
Exp Dermatol. 2018 Dec;27(12):1315-1321. doi: 10.1111/exd.13792.
4
Efficient killing of tumor cells by CAR-T cells requires greater number of engaged CARs than TCRs.CAR-T 细胞要更有效地杀死肿瘤细胞,需要比 TCR 更多的结合 CAR。
J Biol Chem. 2021 Sep;297(3):101033. doi: 10.1016/j.jbc.2021.101033. Epub 2021 Aug 8.
5
Tandem CAR-T cells targeting CD70 and B7-H3 exhibit potent preclinical activity against multiple solid tumors.双靶点 CAR-T 细胞(靶向 CD70 和 B7-H3)针对多种实体瘤表现出强大的临床前活性。
Theranostics. 2020 Jun 18;10(17):7622-7634. doi: 10.7150/thno.43991. eCollection 2020.
6
Chimeric antigen receptor (CAR)-T-cell therapy in non-small-cell lung cancer (NSCLC): current status and future perspectives.嵌合抗原受体 (CAR)-T 细胞疗法在非小细胞肺癌 (NSCLC) 中的应用:现状与未来展望。
Cancer Immunol Immunother. 2021 Mar;70(3):619-631. doi: 10.1007/s00262-020-02735-0. Epub 2020 Oct 6.
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Chimeric Antigen Receptor (CAR) T Cell Therapy for Metastatic Melanoma: Challenges and Road Ahead.嵌合抗原受体 (CAR) T 细胞疗法治疗转移性黑色素瘤:挑战与展望。
Cells. 2021 Jun 9;10(6):1450. doi: 10.3390/cells10061450.
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Chimeric antigen receptor therapy in hematological malignancies: antigenic targets and their clinical research progress.嵌合抗原受体疗法在血液恶性肿瘤中的应用:抗原靶点及其临床研究进展。
Ann Hematol. 2020 Aug;99(8):1681-1699. doi: 10.1007/s00277-020-04020-7. Epub 2020 May 9.
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In Vitro-Transcribed mRNA Chimeric Antigen Receptor T Cell (IVT mRNA CAR T) Therapy in Hematologic and Solid Tumor Management: A Preclinical Update.体外转录信使 RNA 嵌合抗原受体 T 细胞(IVT mRNA CAR T)疗法在血液系统恶性肿瘤和实体瘤治疗中的临床前进展。
Int J Mol Sci. 2020 Sep 6;21(18):6514. doi: 10.3390/ijms21186514.
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Clinical investigation of CAR T cells for solid tumors: Lessons learned and future directions.嵌合抗原受体 T 细胞治疗实体瘤的临床研究:经验总结与未来方向。
Pharmacol Ther. 2020 Jan;205:107419. doi: 10.1016/j.pharmthera.2019.107419. Epub 2019 Oct 16.

引用本文的文献

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[CAR-T cells in Dermatology: Mechanisms of action and applications in autoimmune diseases].[皮肤科中的嵌合抗原受体T细胞:自身免疫性疾病中的作用机制与应用]
Rev Med Inst Mex Seguro Soc. 2025 Mar 3;63(2):e6626. doi: 10.5281/zenodo.14617135.
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Global trends and emerging insights in BRAF and MEK inhibitor resistance in melanoma: a bibliometric analysis.黑色素瘤中BRAF和MEK抑制剂耐药的全球趋势与新见解:一项文献计量分析
Front Mol Biosci. 2025 Jan 17;12:1538743. doi: 10.3389/fmolb.2025.1538743. eCollection 2025.
3
CRISPR/Cas9 system: a novel approach to overcome chemotherapy and radiotherapy resistance in cancer.
CRISPR/Cas9系统:一种克服癌症化疗和放疗耐药性的新方法。
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):3373-3408. doi: 10.1007/s00210-024-03480-2. Epub 2024 Nov 19.
4
Immunotherapy and delivery systems for melanoma.黑素瘤的免疫疗法和递药系统。
Hum Vaccin Immunother. 2024 Dec 31;20(1):2394252. doi: 10.1080/21645515.2024.2394252. Epub 2024 Sep 17.
5
The development of chimeric antigen receptor T-cells against CD70 for renal cell carcinoma treatment.嵌合抗原受体 T 细胞针对肾细胞癌治疗的 CD70 的开发。
J Transl Med. 2024 Apr 18;22(1):368. doi: 10.1186/s12967-024-05101-1.
6
TIL-Derived CAR T Cells Improve Immune Cell Infiltration and Survival in the Treatment of CD19-Humanized Mouse Colorectal Cancer.肿瘤浸润淋巴细胞来源的嵌合抗原受体T细胞在治疗CD19人源化小鼠结直肠癌中可改善免疫细胞浸润和生存期。
Cancers (Basel). 2023 Nov 24;15(23):5567. doi: 10.3390/cancers15235567.
7
Combining CSPG4-CAR and CD20-CCR for treatment of metastatic melanoma.联合 CSPG4-CAR 和 CD20-CCR 治疗转移性黑色素瘤。
Front Immunol. 2023 Oct 11;14:1178060. doi: 10.3389/fimmu.2023.1178060. eCollection 2023.
8
Immunogenic Cell Death Enhances Immunotherapy of Diffuse Intrinsic Pontine Glioma: From Preclinical to Clinical Studies.免疫原性细胞死亡增强弥漫性脑桥内在胶质瘤的免疫治疗:从临床前研究到临床研究
Pharmaceutics. 2022 Aug 24;14(9):1762. doi: 10.3390/pharmaceutics14091762.
9
Opportunities and obstacles for the melanoma immunotherapy using T cell and chimeric antigen receptor T (CAR-T) applications: a literature review.利用 T 细胞和嵌合抗原受体 T(CAR-T)应用进行黑色素瘤免疫治疗的机遇与挑战:文献综述。
Mol Biol Rep. 2022 Nov;49(11):10627-10633. doi: 10.1007/s11033-022-07633-5. Epub 2022 Jun 18.
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Immunotherapy for HER2-Positive Breast Cancer: Clinical Evidence and Future Perspectives.HER2阳性乳腺癌的免疫治疗:临床证据与未来展望。
Cancers (Basel). 2022 Apr 25;14(9):2136. doi: 10.3390/cancers14092136.