外科理论与实践

外科理论与实践 >

2023 , Vol. 28 >Issue 05: 483 - 487

DOI: https://doi.org/10.16139/j.1007-9610.2023.05.15

综述

CAR-T细胞免疫治疗结肠直肠癌的研究现状与展望

展开
  • 海军军医大学长海医院肛肠外科，上海 200433

收稿日期: 2022-11-18

  网络出版日期: 2024-01-04

基金资助

上海申康医院发展中心第二轮《促进市级医院临床技能与临床创新三年行动计划》研究型医师创新转化能力培训项目(SHDC2022CRT007)

收起

Current status and prospect of CAR-T cell immunotherapy for colorectal cancer

Expand
  • Department of Colorectal Surgery, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China

Received date: 2022-11-18

  Online published: 2024-01-04

Fold

摘要

嵌合抗原受体T细胞（chimeric antigen receptor T cell, CAR-T细胞）免疫治疗是肿瘤治疗的全新方法，在血液肿瘤的治疗中获得显著成效。结肠直肠癌（colorectal cancer, CRC）作为实体肿瘤，具有与血液肿瘤不同的特性，这对CART细胞免疫治疗靶点的选取及治疗效果都存在着一定制约。因此，需根据CRC的特征选择特异性高和有效性强的治疗靶点，同时还需突破治疗产生的不良反应及实体肿瘤微环境等限制因素，使该疗法在CRC治疗中得以应用。本文旨在归纳CAR-T细胞免疫治疗CRC选择治疗靶点的策略，分析该治疗方式治疗CRC的制约因素，并展望CAR-T细胞免疫治疗CRC的前景。

关键词： 嵌合抗原受体T细胞; 结肠直肠癌; 免疫治疗

本文引用格式

张天帅, 周乐其 综述, 于冠宇, 张卫 审校 . CAR-T细胞免疫治疗结肠直肠癌的研究现状与展望[J]. 外科理论与实践, 2023 , 28(05) : 483 -487 . DOI: 10.16139/j.1007-9610.2023.05.15

Abstract

Chimeric antigen receptor T (CAR-T) cell therapy is a new method of immunotherapy for cancer that has achieved remarkable results in treating blood tumors. However, colorectal cancer(CRC), as a solid tumor, has different characteristics from hematological tumors, which impose certain constraints on the selection of its therapeutic targets and the effectiveness of treatment of CAR-T therapy. Therefore, it is necessary to select therapeutic targets with high specificity and effectiveness according to the characteristics of CRC, as well as to break through the constraints such as adverse effects caused by the treatment and the solid tumor microenvironment, to make CAR-T therapy applicable in the treatment of CRC. This article aimed to summarize the strategy of selecting therapeutic targets for CAR-T cell immunotherapy for CRC, analyze the restrictive factors of this therapy in the treatment of CRC, and forecast the prospect of CAR-T cell immunotherapy for CRC.

Key words： Chimeric antigen receptor T cell; Colorectal cancer; Immunotherapy

参考文献

[1] SUNG H, FERLAY J, SIEGEL R L, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3):209-249.
[2] SIDDIQUI R S, SARDAR M. A systematic review of the role of chimeric antigen receptor T (CAR-T) cell therapy in the treatment of solid tumors[J]. Cureus, 2021, 13(4):e14494.
[3] COUZIN-FRANKEL J. Breakthrough of the year 2013.Cancer immunotherapy[J]. Science, 2013, 342(6165):1432-1433.
[4] STERNER R C, STERNER R M. CAR-T cell therapy: current limitations and potential strategies[J]. Blood Cancer J, 2021, 11(4):69.
[5] QI C, GONG J, LI J, et al. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results[J]. Nat Med, 2022, 28(6):1189-1198.
[6] SUR D, HAVASI A, CAINAP C, et al. Chimeric antigen receptor T-cell therapy for colorectal cancer[J]. J Clin Med, 2020, 9(1):182.
[7] CREES Z D, GHOBADI A. Cellular therapy updates in B-cell lymphoma: the state of the CAR-T[J]. Cancers (Basel), 2021, 13(20):5181.
[8] MARTINEZ M, MOON E K. CAR T cells for solid tumors: new strategies for finding, infiltrating, and surviving in the tumor microenvironment[J]. Front Immunol, 2019, 10:128.
[9] SNOOK A E, MAGEE M S, WALDMAN S A. GUCY2C-targeted cancer immunotherapy: past, present and future[J]. Immunol Res, 2011, 51(2-3):161-169.
[10] MAGEE M S, ABRAHAM T S, BAYBUTT T R, et al. Human GUCY2C-targeted chimeric antigen receptor (CAR)-expressing T cells eliminate colorectal cancer metastases[J]. Cancer Immunol Res, 2018, 6(5):509-516.
[11] HAMMARSTR?M S. The carcinoembryonic antigen(CEA) family: structures, suggested functions and expression in normal and malignant tissues[J]. Semin Cancer Biol, 1999, 9(2):67-81.
[12] HALL C, CLARKE L, PAL A, et al. A review of the role of carcinoembryonic antigen in clinical practice[J]. Ann Coloproctol, 2019, 35(6):294-305.
[13] XU J, MENG Q, SUN H, et al. HER2-specific chimeric antigen receptor-T cells for targeted therapy of metastatic colorectal cancer[J]. Cell Death Dis, 2021, 12(12):1109.
[14] LI W, ZHOU Y, WU Z, et al. Targeting Wnt signaling in the tumor immune microenvironment to enhancing EpCAM CAR T-Cell therapy[J]. Front Pharmacol, 2021, 12:724306.
[15] ZHANG B L, LI D, GONG Y L, et al. Preclinical evaluation of chimeric antigen receptor-modified T cells specific to epithelial cell adhesion molecule for treating colorectal cancer[J]. Hum Gene Ther, 2019, 30(4):402-412.
[16] DARCY P K, HAYNES N M, SNOOK M B, et al. Redirected perforin-dependent lysis of colon carcinoma by ex vivo genetically engineered CTL[J]. J Immunol, 2000, 164(7):3705-3712.
[17] ZHANG C, WANG Z, YANG Z, et al. Phase I escalating-dose trial of CAR-T therapy targeting CEA(+) metastatic colorectal cancers[J]. Mol Ther, 2017, 25(5):1248-1258.
[18] MORELLO A, SADELAIN M, ADUSUMILLI P S. Mesothelin-targeted CARs: driving T cells to solid tumors[J]. Cancer Discov, 2016, 6(2):133-146.
[19] ZHANG Q, LIU G, LIU J, et al. The antitumor capacity of mesothelin-CAR-T cells in targeting solid tumors in mice[J]. Mol Ther Oncolytics, 2021, 20:556-568.
[20] FREY N, PORTER D. Cytokine release syndrome with chimeric antigen receptor T cell therapy[J]. Biol Blood Marrow Transplant, 2019, 25(4):e123-e127.
[21] FREYER C W, PORTER D L. Cytokine release syndrome and neurotoxicity following CAR T-cell therapy for hematologic malignancies[J]. J Allergy Clin Immunol, 2020, 146(5):940-948.
[22] AHMED N, BRAWLEY V S, HEGDE M, et al. Human epidermal growth factor receptor 2 (HER2) -specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma[J]. J Clin Oncol, 2015, 33(15):1688-1696.
[23] MORGAN R A, YANG J C, Kitano M, et al. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2[J]. Mol Ther, 2010, 18(4):843-851.
[24] PARKHURST M R, YANG J C, Langan R C, et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis[J]. Mol Ther, 2011, 19(3):620-626.
[25] BHOWMICK N A, NEILSON E G, Moses H L. Stromal fibroblasts in cancer initiation and progression[J]. Nature, 2004, 432(7015):332-337.
[26] LIU G, RUI W, ZHAO X, et al. Enhancing CAR-T cell efficacy in solid tumors by targeting the tumor microenvironment[J]. Cell Mol Immunol, 2021, 18(5):1085-1095.
[27] BIFFI G, TUVESON D A. Diversity and biology of cancer-associated fibroblasts[J]. Physiol Rev, 2021, 101(1):147-176.
[28] CHEN Y, ZHENG X, WU C. The role of the tumor microenvironment and treatment strategies in colorectal cancer[J]. Front Immunol, 2021, 12:792691.
[29] DE JAEGHERE E A, DENYS H G, DE WEVER O. Fibroblasts fuel immune escape in the tumor microenvironment[J]. Trends Cancer, 2019, 5(11):704-723.
[30] JAHANAFROOZ Z, MOSAFER J, AKBARI M, et al. Colon cancer therapy by focusing on colon cancer stem cells and their tumor microenvironment[J]. J Cell Physiol, 2020, 235(5):4153-4166.
[31] HASAN M N, CAPUK O, PATEL S M, et al. The role of metabolic plasticity of tumor-associated macrophages in shaping the tumor microenvironment immunity[J]. Cancers(Basel), 2022, 14(14):3331.
[32] SCOTT E N, GOCHER A M, WORKMAN C J, et al. Regulatory T cells: barriers of immune infiltration into the tumor microenvironment[J]. Front Immunol, 2021, 12:702726.
[33] TIAN Y, LI Y, SHAO Y, et al. Gene modification strategies for next-generation CAR T cells against solid cancers[J]. J Hematol Oncol, 2020, 13(1):54.
[34] GOLUBOVSKAYA V, BERAHOVICH R, ZHOU H, et al. CD47-CAR-T cells effectively kill target cancer cells and block pancreatic tumor growth[J]. Cancers (Basel), 2017, 9(10):139.
[35] WILKIE S, VAN SCHALKWYK M C, HOBBS S, et al. Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling[J]. J Clin Immunol, 2012, 32(5):1059-1070.
[36] CARUANA I, SAVOLDO B, HOYOS V, et al. Hepara-nase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes[J]. Nat Med, 2015, 21(5):524-529.
[37] WANG L C, LO A, SCHOLLER J, et al. Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity[J]. Cancer Immunol Res, 2014, 2(2):154-166.
[38] HILTBRUNNER S, BRITSCHGI C, SCHUBERTH P, et al. Local delivery of CAR T cells targeting fibroblast activation protein is safe in patients with pleural mesothelioma: first report of FAPME, a phase Ⅰ clinical trial[J]. Ann Oncol, 2021, 32(1):120-121.
[39] BURGA R A, THORN M, POINT G R, et al. Liver myeloid-derived suppressor cells expand in response to liver metastases in mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T[J]. Cancer Immunol Immunother, 2015, 64(7):817-829.
Options
文章导航

/

〈 〉