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结直肠癌中的过继性细胞疗法:嵌合抗原受体T细胞的进展

Adoptive cell therapy in colorectal cancer: Advances in chimeric antigen receptor T cells.

作者信息

Chen Meng-Yan, Wang Chen, Wang Yu-Gang, Shi Min

机构信息

Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.

出版信息

World J Gastrointest Oncol. 2025 Jul 15;17(7):106723. doi: 10.4251/wjgo.v17.i7.106723.


DOI:10.4251/wjgo.v17.i7.106723
PMID:40697242
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12278228/
Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide and remains a major treatment challenge, particularly in advanced and metastatic stages. Current standard treatments have limited efficacy, underscoring the urgent need for innovative strategies. Adoptive cell therapy (ACT), which involves expansion or genetic engineering of immune cells, is a promising approach to bolster anti-tumor immune responses. Key ACT modalities include chimeric antigen receptor (CAR) T cells, tumor-infiltrating lymphocytes (TILs), and T cell receptor (TCR)-engineered T cells. CAR-T cell therapy has shown success in hematological malignancies but faces significant challenges in solid tumors like CRC. These challenges include antigen heterogeneity, an immunosuppressive tumor microenvironment, on-target off-tumor toxicity, among other factors. To address these limitations, combinatorial approaches, such as immune checkpoint inhibitors, cytokines, and advanced gene-editing tools like CRISPR/Cas9, are being actively explored. These strategies aim to enhance CAR-T cell specificity, improve resistance to immunosuppressive signals, and optimize functionality. This review summarizes ACT approaches for CRC, with a focus on CAR-T therapy. It briefly introduces TILs and TCR-T cells, while emphasizing the major challenges faced by CAR-T therapy in solid tumors and discusses potential strategies to improve therapeutic outcomes.

摘要

结直肠癌(CRC)是全球第三大常见癌症,仍然是一个重大的治疗挑战,尤其是在晚期和转移阶段。目前的标准治疗方法疗效有限,凸显了对创新策略的迫切需求。过继性细胞疗法(ACT)涉及免疫细胞的扩增或基因工程改造,是增强抗肿瘤免疫反应的一种有前景的方法。关键的ACT模式包括嵌合抗原受体(CAR)T细胞、肿瘤浸润淋巴细胞(TILs)和T细胞受体(TCR)工程化T细胞。CAR-T细胞疗法在血液系统恶性肿瘤中已显示出成效,但在像CRC这样的实体瘤中面临重大挑战。这些挑战包括抗原异质性、免疫抑制性肿瘤微环境、靶向非肿瘤毒性等因素。为了解决这些局限性,正在积极探索联合方法,如免疫检查点抑制剂、细胞因子以及像CRISPR/Cas9这样的先进基因编辑工具。这些策略旨在提高CAR-T细胞的特异性、增强对免疫抑制信号的抗性并优化其功能。本综述总结了用于CRC的ACT方法,重点是CAR-T疗法。它简要介绍了TILs和TCR-T细胞,同时强调了CAR-T疗法在实体瘤中面临的主要挑战,并讨论了改善治疗效果的潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ac/12278228/236033fea199/wjgo-17-7-106723-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ac/12278228/09e99772bbf6/wjgo-17-7-106723-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ac/12278228/dbd5c315c760/wjgo-17-7-106723-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ac/12278228/fa47c7b34cee/wjgo-17-7-106723-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ac/12278228/236033fea199/wjgo-17-7-106723-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ac/12278228/09e99772bbf6/wjgo-17-7-106723-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ac/12278228/dbd5c315c760/wjgo-17-7-106723-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ac/12278228/fa47c7b34cee/wjgo-17-7-106723-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ac/12278228/236033fea199/wjgo-17-7-106723-g004.jpg

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Adoptive cell therapy in colorectal cancer: Advances in chimeric antigen receptor T cells.

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本文引用的文献

[1]
Novel strategies to manage CAR-T cell toxicity.

Nat Rev Drug Discov. 2025-5

[2]
Chimeric Antigen Receptor-T Cells in Colorectal Cancer: Pioneering New Avenues in Solid Tumor Immunotherapy.

J Clin Oncol. 2025-3-10

[3]
XCL1-secreting CEA CAR-T cells enhance endogenous CD8 T cell responses to tumor neoantigens to confer a long-term antitumor immunity.

J Immunother Cancer. 2025-1-6

[4]
Repurposing anti-mesothelin CAR-NK immunotherapy against colorectal cancer.

J Transl Med. 2024-12-4

[5]
Persistence of activated anti-mesothelin hYP218 chimeric antigen receptor T cells in the tumour is associated with efficacy in gastric and colorectal carcinomas.

Clin Transl Med. 2024-11

[6]
GPA33 expression in colorectal cancer can be induced by WNT inhibition and targeted by cellular therapy.

Oncogene. 2025-1

[7]
CD8α Structural Domains Enhance GUCY2C CAR-T Cell Efficacy.

Cancer Biol Ther. 2024-12-31

[8]
Chimeric Antigen Receptor T Cells Targeting CD19 and GCC in Metastatic Colorectal Cancer: A Nonrandomized Clinical Trial.

JAMA Oncol. 2024-11-1

[9]
Enhanced tumor response to adoptive T cell therapy with PHD2/3-deficient CD8 T cells.

Nat Commun. 2024-9-6

[10]
Engineered T cells for Colorectal Cancer.

Immunotherapy. 2024

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