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中华普通外科学文献(电子版) ›› 2021, Vol. 15 ›› Issue (02) : 152 -156. doi: 10.3877/cma.j.issn.1674-0793.2021.02.017

所属专题: 文献

综述

TCR-T细胞免疫疗法治疗肝细胞癌的研究现状及策略
胡伟1, 何美芳2,()   
  1. 1. 510080 广州,中山大学附属第一医院肿瘤中心
    2. 510080 广州,中山大学附属第一医院外科实验室
  • 收稿日期:2020-09-30 出版日期:2021-04-01
  • 通信作者: 何美芳
  • 基金资助:
    中山大学青年教师培育项目(19ykpy60)

Research status and strategy of TCR-T cell immunotherapy for hepatocellular carcinoma

Wei Hu1, Meifang He2,()   

  1. 1. Tumor Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
    2. Surgical Laboratory, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
  • Received:2020-09-30 Published:2021-04-01
  • Corresponding author: Meifang He
引用本文:

胡伟, 何美芳. TCR-T细胞免疫疗法治疗肝细胞癌的研究现状及策略[J/OL]. 中华普通外科学文献(电子版), 2021, 15(02): 152-156.

Wei Hu, Meifang He. Research status and strategy of TCR-T cell immunotherapy for hepatocellular carcinoma[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2021, 15(02): 152-156.

肝细胞癌是原发性肝癌的主要病理类型,目前的临床治疗方法难以达到理想的效果,迫切需要探索新的、有效的治疗方法。T细胞受体基因工程改造T细胞(TCR-T)疗法因在实体瘤中的成功应用,被认为是最有前景的免疫治疗方式之一。本文主要从TCR-T治疗在肝细胞癌中的研究进展进行综述,并针对性提出一些解决策略,包括优化TCR亲和力、降低毒性反应、减少外源性和内源性TCR双链错配、改善肿瘤微环境、促进TCR-T细胞扩增。

Hepatocellular carcinoma (HCC) is the main form of liver cancer, and it is difficult to achieve the desirable effect for the current clinical treatment methods. Therefore, it is urgent to explore new and effective treatment methods. T cell receptor-gene engineered T cells (TCR-T) therapy has been proved to be a great promising immunotherapy because of its successful application in solid tumors. In this review, we focus on the occurrence, development and application of TCR-T immunotherapy in HCC. Some strategies are proposed, including optimizing TCR affinity, reducing toxicity, reducing mismatch of double strand in exogenous and endogenous TCR, improving tumor microenvironment, and promoting TCR-T cell expansion.

表1 TCR-T细胞治疗肝细胞癌的临床试验
[1]
Global Burden of Disease Cancer C, Fitzmaurice C, Allen C, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the global burden of disease study[J]. JAMA Oncol 2017, 3: 524-548.
[2]
Caraballo Galva LD, Cai L, Shao Y, et al. Engineering T cells for immunotherapy of primary human hepatocellular carcinoma[J]. J Genet Genomics, 2020, 47(1): 1-15.
[3]
Docta RY, Ferronha T, Sanderson JP, et al. Tuning T-Cell receptor affinity to optimize clinical risk-benefit when targeting alpha-fetoprotein-positive liver cancer[J]. Hepatology, 2019, 69(5): 2061-2075.
[4]
Zhu W, Peng Y, Wang L, et al. Identification of α-fetoprotein-specific T-cell receptors for hepatocellular carcinoma immuno-therapy[J]. Hepatology, 2018, 68(2): 574-589.
[5]
Rosati SF, Parkhurst MR, Hong Y, et al. A novel murine T-cell receptor targeting NY-ESO-1[J]. J Immunother, 2014, 37(3): 135-146.
[6]
Li Y, Moysey R, Molloy PE, et al. Directed evolution of human T-cell receptors with picomolar affinities by phage display[J]. Nat Biotechnol, 2005, 23(3): 349-354.
[7]
Robbins PF, Li YF, El-Gamil M, et al. Single and dual amino acid substitutions in TCR CDRs can enhance antigen-specific T cell functions[J]. J Immunol, 2008, 180(9): 6116-6131.
[8]
Gehring AJ, Xue SA, Ho ZZ, et al. Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellular carcinoma cell lines[J]. J Hepatol, 2011, 55(1): 103-110.
[9]
Qasim W, Brunetto M, Gehring AJ, et al. Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient[J]. J Hepatol, 2015, 62(2): 486-491.
[10]
Nakagawa H, Mizukoshi E, Kobayashi E, et al. Association between high-avidity T-cell receptors, induced by α-fetoprotein-derived peptides, and anti-tumor effects in patients with hepatocellular carcinoma[J]. Gastroenterology, 2017, 152(6): 1395-1406. e10.
[11]
Zhang HH, Mei MH, Fei R, et al. Regulatory T cell depletion enhances tumor specific CD8 T-cell responses, elicited by tumor antigen NY-ESO-1b in hepatocellular carcinoma patients, in vitro[J]. Int J Oncol, 2010, 36(4): 841-848.
[12]
Dargel C, Bassani-Sternberg M, Hasreiter J, et al. T cells engineered to express a T-cell receptor specific for glypican-3 to recognize and kill hepatoma cells in vitro and in mice[J]. Gastroenterology, 2015, 149(4): 1042-1052.
[13]
Spear TT, Callender GG, Roszkowski JJ, et al. TCR gene-modified T cells can efficiently treat established hepatitis C-associated hepatocellular carcinoma tumors[J]. Cancer Immunol Immunother, 2016, 65(3): 293-304.
[14]
Morgan RA, Chinnasamy N, Abate-Daga D, et al. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy[J]. J Immunother, 2013, 36(2): 133-151.
[15]
Di Stasi A, Tey SK, Dotti G, et al. Inducible apoptosis as a safety switch for adoptive cell therapy[J]. N Engl J Med, 2011, 365(18): 1673-1683.
[16]
Scholten KB, Kramer D, Kueter EW, et al. Codon modification of T cell receptors allows enhanced functional expression in transgenic human T cells[J]. Clin Immunol, 2006, 119(2): 135-145.
[17]
Okamoto S, Mineno J, Ikeda H, et al. Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR[J]. Cancer Res, 2009, 69(23): 9003-9011.
[18]
Cohen CJ, Li YF, El-Gamil M, et al. Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond[J]. Cancer Res, 2007, 67(8): 3898-3903.
[19]
Chang HC, Bao Z, Yao Y, et al. A general method for facilitating heterodimeric pairing between two proteins: application to expression of alpha and beta T-cell receptor extracellular segments[J]. Proc Natl Acad Sci U S A, 1994, 91(24): 11408-11412.
[20]
Jindal A, Thadi A, Shailubhai K. Hepatocellular carcinoma: etiology and current and future drugs[J]. J Clin Exp Hepatol, 2019, 9(2): 221-232.
[21]
Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation[J]. J Exp Med, 2000, 192(7): 1027-1034.
[22]
Zhang L, Davies JS, Serna C, et al. Enhanced efficacy and limited systemic cytokine exposure with membrane-anchored interleukin-12 T-cell therapy in murine tumor models[J]. J Immunother Cancer, 2020, 8(1): e000210.
[23]
Craddock JA, Lu A, Bear A, et al. Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b[J]. J Immunother, 2010, 33(8): 780-788.
[24]
Sadelain M. T-cell engineering for cancer immunotherapy[J]. Cancer J, 2009, 15(6): 451-455.
[25]
Brentjens RJ, Latouche JB, Santos E, et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15[J]. Nat Med, 2003, 9(3): 279-286.
[26]
Murga-Zamalloa C, Rolland D, Polk A, et al. Colony-stimulating factor 1 receptor (CSF1R) activates AKT/mTOR signaling and promotes T-Cell lymphoma viability[J]. Clin Cancer Res, 2020, 26(3): 690-703.
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