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Recent updates on chimeric antigen receptor T cell therapy for hepatocellular carcinoma

Cancer Gene Therapy volume 28, pages 1075–1087 (2021)Cite this article

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Abstract

Chimeric antigen receptor T cell (CAR-T) therapy is novel tumor immunotherapy that enables T cells to specifically recognize tumor-associated antigens through genetic engineering technology, thus exerting antitumor effects, and it has achieved encouraging outcomes in leukemia and lymphoma. Building on excellent progress, CAR-T therapy is also expected to work well in solid tumors. Hepatocellular carcinoma (HCC), the most common primary liver cancer, is usually diagnosed at an advanced stage. Current management options for HCC remain limited, and although previous studies have indicated the feasibility of CAR-T cells, ideal therapeutic effects have not yet been achieved. This is, in part, due to the heterogeneity of tumor antigens, high intratumor pressure, immunosuppressive microenvironment, CAR-T cell exhaustion, and serious adverse reactions, which compromise the therapeutic efficiency of CAR-T immunotherapy in HCC. To overcoming these challenges, many ongoing preclinical and clinical studies were conducted. This review summarizes current CAR-T therapy targets in the treatment of HCC, discusses current obstacles and possible solutions in the process, and describes potential strategies to improve the efficacy of CAR-T cells for patients with HCC.

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Fig. 1: Summary of strategies to improve the efficacy of CAR-T cells for patients with HCC.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  2. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301–14.

    Article  PubMed  Google Scholar 

  3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30.

    Article  PubMed  Google Scholar 

  4. Yu JX, Hubbard-Lucey VM, Tang J. The global pipeline of cell therapies for cancer. Nat Rev Drug Discov. 2019;18:821–2.

    Article  CAS  Google Scholar 

  5. Efficace F, Vignetti M. Quality of life and CAR-T cell therapy in children, adolescents, and young adults with haematological malignancies. Lancet Oncol. 2019;20:1625–6.

    Article  PubMed  Google Scholar 

  6. O’Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K, Morrissette JJD, et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017;9:a984.

    Article  Google Scholar 

  7. Yu JY, Wu XW, Yan JY, Yu H, Xu LW, Chi ZH, et al. Anti-GD2/4-1BB chimeric antigen receptor T cell therapy for the treatment of Chinese melanoma patients. J Hematol Oncol. 2018;11:1.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zheng ZQ, Tang Q, Feng ZQ. CAR-T cell therapy and its application in clinical cancer treatment. Asia-Pac J Blood Types Genes. 2017;1:1–6.

    Google Scholar 

  9. Sun B, Yang D, Dai HJ, Liu XY, Jia R, Cui XY, et al. Eradication of Hepatocellular Carcinoma by NKG2D-Based CAR-T Cells. Cancer Immunol Res. 2019;7:1813–23.

    Article  CAS  PubMed  Google Scholar 

  10. Xu YR, Zhou Y, Tang Q, Liu ZY, Huang XC, Yang TT, et al. Construction of Trop-2-targeted chimeric antigen receptor-modified T cells and their effects on the proliferation of ovarian cancer cells in vitro. Acta Universitatis Medicinalis Nanjing. 2017;37:653–8.

    Google Scholar 

  11. Nakatsura T, Yoshitake Y, Senju S, Monji M, Komori H, Motomura Y, et al. Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker. Biochem Biophys Res Commun. 2003;306:16–25.

    Article  CAS  PubMed  Google Scholar 

  12. Capurro M, Wanless IR, Sherman M, Deboer G, Shi W, Miyoshi E, et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology. 2003;125:89–97.

    Article  CAS  PubMed  Google Scholar 

  13. Zhou FB, Shang WT, Yu XL, Tian J. Glypican-3: a promising biomarker for hepatocellular carcinoma diagnosis and treatment. Med Res Rev. 2018;38:741–67.

    Article  CAS  PubMed  Google Scholar 

  14. Stadlmann S, Gueth U, Baumhoer D, Moch H, Terracciano L, Singer G. Glypican-3 expression in primary and recurrent ovarian carcinomas. Int J Gynecol Pathol. 2007;26:341–4.

    Article  PubMed  Google Scholar 

  15. Aviel-Ronen S, Lau SK, Pintilie M, Lau D, Liu N, Tsao MS, et al. Glypican-3 is overexpressed in lung squamous cell carcinoma, but not in adenocarcinoma. Mod Pathol. 2008;21:817–25.

    Article  CAS  PubMed  Google Scholar 

  16. Kandil D, Leiman G, Allegretta M, Evans M. Glypican-3 protein expression in primary and metastatic melanoma: a combined immunohistochemistry and immunocytochemistry study. Cancer 2009;117:271–8.

    CAS  PubMed  Google Scholar 

  17. Montalbano M, Rastellini C, McGuire JT, Prajapati J, Shirafkan A, Vento R, et al. Role of Glypican-3 in the growth, migration and invasion of primary hepatocytes isolated from patients with hepatocellular carcinoma. Cell Oncol. 2018;41:169–84.

    Article  CAS  Google Scholar 

  18. Gao HP, Li K, Tu H, Pan XR, Jiang H, Shi BZ, et al. Development of T cells redirected to glypican-3 for the treatment of hepatocellular carcinoma. Clin Cancer Res. 2014;20:6418–28.

    Article  CAS  PubMed  Google Scholar 

  19. Jiang ZW, Jiang XF, Chen SM, Lai YX, Wei XR, Li BH, et al. Anti-GPC3-CAR T cells suppress the growth of tumor cells in patient-derived xenografts of hepatocellular carcinoma. Front Immunol. 2016;7:690.

    PubMed  Google Scholar 

  20. Gillespie JR, Uversky VN. Structure and function of α-fetoprotein: a biophysical overview. Biochim Biophys Acta. 2000;1480:41–56.

    Article  CAS  PubMed  Google Scholar 

  21. Liu H, Xu YY, Xiang JY, Long L, Green S, Yang ZY, et al. Targeting alpha-fetoprotein (AFP)–MHC complex with CAR T-cell therapy for liver cancer. Clin Cancer Res. 2017;23:478–88.

    Article  CAS  PubMed  Google Scholar 

  22. Migliore C, Giordano S. Molecular cancer therapy: can our expectation be MET? Eur J Cancer. 2008;44:641–51.

    Article  CAS  PubMed  Google Scholar 

  23. Eder JP, Vande Woude GF, Boerner SA, LoRusso PM. Novel therapeutic inhibitors of the c-Met signaling pathway in cancer. Clin Cancer Res. 2009;15:2207–14.

    Article  CAS  PubMed  Google Scholar 

  24. Huh CG, Factor VM, Sanchez A, Uchida K, Conner EA, Thorgeirsson SS. Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc Natl Acad Sci USA. 2004;101:4477–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Borowiak M, Garratt AN, Wustefeld T, Strehle M, Trautwein C, Birchmeier C. Met provides essential signals for liver regeneration. Proc Natl Acad Sci USA. 2004;101:10608–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Qi XS, Guo XZ, Han GH, Li HY, Chen J. MET inhibitors for treatment of advanced hepatocellular carcinoma: a review. World J Gastroenterol. 2015;21:5445–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Huang XC. Fabrication of c-Met Chimeric antigen receptor T cells and killing of hepatocellular carcinoma cells in vitro and in vivo. Nanjing Medical University; 2018.

  28. Li T, Jiang W, Gu X, Li B, Wang JJ, Shi X, et al. Optimization, construction and biological characterization of novel bispecific c-Met/PD-L1 scFv-Fc fusion protein. Acta Universitatis Medicinalis Nanjing. 2019;39:1415–20.

    Google Scholar 

  29. Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer. 2009;9:874–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang J, Liu GM, Li QS, Wang F, Xie F, Zhai RP, et al. Mucin1 promotes the migration and invasion of hepatocellular carcinoma cells via JNK-mediated phosphorylation of Smad2 at the C-terminal and linker regions. Oncotarget. 2015;6:19264–78.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ma YD, Wang Z, Gong RZ, Li LF, Wu HP, Jin HJ, et al. Specific cytotoxicity of MUC1 chimeric antigen receptor-engineered Jurkat T cells against hepatocellular carcinoma. Academic J Second Mil Med Univ. 2014;35:1177–82.

    Article  Google Scholar 

  32. Terris B, Cavard C, Perret C. EpCAM, a new marker for cancer stem cells in hepatocellular carcinoma. J Hepatol. 2010;52:280–1.

    Article  CAS  PubMed  Google Scholar 

  33. Yamashita T, Forgues M, Wang W, Kim JW, Ye QH, Jia HL, et al. EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res. 2008;68:1451–61.

    Article  CAS  PubMed  Google Scholar 

  34. Zhang BL, Li D, Gong YL, Huang Y, Qin DY, Jiang L, et al. Preclinical evaluation of chimeric antigen receptor-modified T cells specific to epithelial cell adhesion molecule for treating colorectal cancer. Hum Gene Ther. 2019;30:402–12.

    Article  CAS  PubMed  Google Scholar 

  35. Ferrandina G, Petrillo M, Bonanno G, Scambia G. Targeting CD133 antigen in cancer. Expert Opin Ther Targets. 2009;13:823–37.

    Article  CAS  PubMed  Google Scholar 

  36. Kohga K, Tatsumi T, Takehara T, Tsunematsu H, Shimizu S, Yamamoto M, et al. Expression of CD133 confers malignant potential by regulating metalloproteinases in human hepatocellular carcinoma. J Hepatol. 2010;52:872–9.

    Article  CAS  PubMed  Google Scholar 

  37. Song W, Li H, Tao K, Li R, Song Z, Zhao Q, et al. Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma. Int J Clin Pract. 2008;62:1212–8.

    Article  CAS  PubMed  Google Scholar 

  38. Wang Y, Chen MX, Wu ZQ, Tong C, Dai HR, Guo YL, et al. CD133-directed CAR T cells for advanced metastasis malignancies: a phase I trial. Oncoimmunology. 2018;7:e1440169.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Li Y, Xu J, Chen L, Zhong WD, Zhang Z, Mi L, et al. HAb18G (CD147), a cancer-associated biomarker and its role in cancer detection. Histopathology. 2009;54:677–87.

    Article  CAS  PubMed  Google Scholar 

  40. Sun JX, Hemler ME. Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res. 2001;61:2276.

    CAS  PubMed  Google Scholar 

  41. Zhu SJ, Li YH, Zhang Y, Wang XX, Gong L, Han XJ, et al. Expression and clinical implications of HAb18G/CD147 in hepatocellular carcinoma. Hepatol Res. 2015;45:97–106.

    Article  CAS  PubMed  Google Scholar 

  42. Fan WZ, Wu YQ, Lu MJ, Yao W, Cui W, Zhao Y, et al. A meta-analysis of the efficacy and safety of iodine [131I] metuximab infusion combined with TACE for treatment of hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 2019;43:451–9.

    Article  CAS  PubMed  Google Scholar 

  43. Bian HJ, Zheng JS, Nan G, Li R, Chen CS, Hu CX, et al. Randomized trial of [131I] metuximab in treatment of hepatocellular carcinoma after percutaneous radiofrequency ablation. J Natl Cancer Inst. 2014;106:dju239.

    Article  PubMed  Google Scholar 

  44. Chen ZN, Mi L, Xu J, Song F, Zhang Q, Zhang Z, et al. Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: clinical Phase I/II trials. Int J Radiat Oncol Biol Phys. 2006;65:435–44.

    Article  CAS  PubMed  Google Scholar 

  45. Zhang RY, Wei D, Liu ZK, Yong YL, Wei W, Zhang ZY, et al. Doxycycline inducible chimeric antigen receptor T cells targeting CD147 for hepatocellular carcinoma therapy. Front Cell Dev Biol. 2019;7:233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Zhang JY, Basher F, Wu JD. NKG2D ligands in tumor immunity: two sides of a coin. Front Immunol. 2015;6:97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Jinushi M, Takehara T, Tatsumi T, Kanto T, Groh V, Spies T, et al. Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid. Int J Cancer. 2003;104:354–61.

    Article  CAS  PubMed  Google Scholar 

  48. Fang L, Gong JY, Wang Y, Liu RG, Li ZS, Wang Z, et al. MICA/B expression is inhibited by unfolded protein response and associated with poor prognosis in human hepatocellular carcinoma. J Exp Clin Cancer Res. 2014;33:76.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Kamimura H, Yamagiwa S, Tsuchiya A, Takamura M, Matsuda Y, Ohkoshi S, et al. Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with early recurrence. J Hepatol. 2011;56:381–8.

    Article  PubMed  Google Scholar 

  50. Sun B, Yang D, Dai HJ, Liu XY, Jia R, Cui XY, et al. Eradication of hepatocellular carcinoma by NKG2D-based CAR-T cells. Cancer Immunol Res. 2019;7:1813–23.

    Article  CAS  PubMed  Google Scholar 

  51. Johnson PJ. The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. Clin Liver Dis. 2001;5:145.

    Article  CAS  PubMed  Google Scholar 

  52. Li T, Jiang W, Ji GZ, Feng ZQ. The research advances of CAR-T cell therapy in solid tumor. J Med Postgr.a 2019;32:886–90.

    Google Scholar 

  53. Zhao W, Jia LZ, Zhang MJ, Huang XC, Qian P, Tang Q, et al. The killing effect of novel bi-specific Trop2/PD-L1 CAR-T cell targeted gastric cancer. Am J Cancer Res. 2019;9:1846.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Chen C, Li KS, Jiang H, Song F, Gao HP, Pan XR, et al. Development of T cells carrying two complementary chimeric antigen receptors against glypican-3 and asialoglycoprotein receptor 1 for the treatment of hepatocellular carcinoma. Cancer Immunol Immunother. 2017;66:475–89.

    Article  CAS  PubMed  Google Scholar 

  55. Liu XJ, Jiang SG, Fang CY, Yang SY, Olalere D, Pequignot EC, et al. Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice. Cancer Res. 2015;75:3596–607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Caruso HG, Hurton LV, Najjar A, Rushworth D, Ang S, Olivares S, et al. Tuning sensitivity of CAR to EGFR density limits recognition of normal tissue while maintaining potent antitumor activity. Cancer Res. 2015;75:3505–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Feng ZQ. Reconsidering CAR-T cell therapy for solid tumors. J Med Postgra. 2019;32:337–40.

    Google Scholar 

  58. Caruana I, Savoldo B, Hoyos V, Weber G, Liu H, Kim ES, et al. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nat Med. 2015;21:524–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kakarla S, Chow KK, Mata M, Shaffer DR, Song XT, Wu MF, et al. Antitumor effects of chimeric receptor engineered human T cells directed to tumor stroma. Mol Ther. 2013;21:1611–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Burga RA, Thorn M, Point GR, Guha P, Nguyen CT, Licata LA, 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. Cancer Immunol Immunother. 2015;64:817–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Katz SC, Burga RA, McCormack E, Wang LJ, Mooring W, Point GR, et al. Phase I hepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor-modified T-cell therapy for CEA+ liver metastases. Clin Cancer Res. 2015;21:3149–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Do HTT, Lee CH, Cho J. Chemokines and their receptors: multifaceted roles in cancer progression and potential value as cancer prognostic markers. Cancers. 2020;12:287.

    Article  CAS  PubMed Central  Google Scholar 

  63. Nagarsheth N, Wicha MS, Zou WP. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol. 2017;17:559–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Liu GN, Rui W, Zheng HL, Huang DS, Yu F, Zhang YW, et al. CXCR2-modified CAR-T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma. Eur J Immunol. 2020;50:712–24.

    Article  CAS  PubMed  Google Scholar 

  65. Gu X, Tang Q. Tumor immune microenvironment: sanctuary of tumor and target for immunotherapy. Asia-Pac J Blood Types Genes. 2018;2:141–8.

    Google Scholar 

  66. Ligtenberg MA, Mougiakakos D, Mukhopadhyay M, Witt K, Lladser A, Chmielewski M, et al. Coexpressed catalase protects chimeric antigen receptor-redirected T cells as well as bystander cells from oxidative stress-induced loss of antitumor activity. J Immunol. 2016;196:759–66.

    Article  CAS  PubMed  Google Scholar 

  67. Newick K, O’Brien S, Sun J, Kapoor V, Maceyko S, Lo A, et al. Augmentation of CAR T-cell trafficking and antitumor efficacy by blocking protein kinase A localization. Cancer Immunol Res. 2016;4:541–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hou AJ, Chang ZL, Lorenzini MH, Zah E, Chen YY. TGF-β-responsive CAR-T cells promote anti-tumor immune function. Bioeng Transl Med. 2018;3:75–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Spear P, Barber A, Rynda-Apple A, Sentman CL. Chimeric antigen receptor T cells shape myeloid cell function within the tumor microenvironment through IFN-γ and GM-CSF. J Immunol. 2012;188:6389–98.

    Article  CAS  PubMed  Google Scholar 

  70. Webb ES, Liu P, Baleeiro R, Lemoine NR, Yuan M, Wang YH. Immune checkpoint inhibitors in cancer therapy. J Biomed Res. 2018;32:317–26.

    PubMed  Google Scholar 

  71. Guo XL, Jiang H, Shi BZ, Zhou M, Zhang HH, Shi ZM, et al. Disruption of PD-1 enhanced the anti-tumor activity of chimeric antigen receptor T cells against hepatocellular carcinoma. Front Pharmacol. 2018;9:1118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Pan ZY, Di SM, Shi BZ, Jiang H, Shi ZM, Liu Y, et al. Increased antitumor activities of glypican-3-specific chimeric antigen receptor-modified T cells by coexpression of a soluble PD1–CH3 fusion protein. Cancer Immunol Immunother. 2018;67:1621–34.

    Article  CAS  PubMed  Google Scholar 

  73. Sasse A, Carmo R. Sorafenib for advanced hepatocellular carcinoma (HCC) in the public health setting in Brazil: a cost-effectiveness analysis. Ann Oncol. 2019;30 Suppl 4:v66.

    Article  Google Scholar 

  74. Wu XQ, Luo H, Shi BZ, Di SM, Sun RX, Su JW, et al. Combined antitumor effects of sorafenib and GPC3-CAR T cells in mouse models of hepatocellular carcinoma. Mol Ther. 2019;27:1483–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wang XL, Walter M, Urak R, Weng LH, Huynh C, Lim L, et al. Lenalidomide enhances the function of CS1 chimeric antigen receptor–redirected T cells against multiple myeloma. Clin Cancer Res. 2018;24:106–19.

    Article  CAS  PubMed  Google Scholar 

  76. Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12:492–9.

    Article  CAS  PubMed  Google Scholar 

  77. Markley JC, Sadelain M. IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell–mediated rejection of systemic lymphoma in immunodeficient mice. Blood. 2010;115:3508–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Liu Y, Di SM, Shi BZ, Zhang HH, Wang Y, Wu XQ, et al. Armored inducible expression of IL-12 enhances antitumor activity of glypican-3-targeted chimeric antigen receptor-engineered T cells in hepatocellular carcinoma. J Immunol. 2019;203:198–207.

    Article  CAS  PubMed  Google Scholar 

  79. Batra SA, Purva R, Linjie G, Amy NC, Julien F, Julien B, et al. Glypican-3-specific CAR T cells co-expressing IL15 and IL21 have superior expansion and antitumor activity against hepatocellular carcinoma. Cancer. Immunol Res. 2020;8:309–20.

    CAS  Google Scholar 

  80. Chmielewski M, Abken H. CAR T cells releasing IL-18 convert to T-Bet high FoxO1 low effectors that exhibit augmented activity against advanced solid tumors. Cell Rep. 2017;21:3205–19.

    Article  CAS  PubMed  Google Scholar 

  81. Ma XC, Shou PS, Smith C, Chen YH, Du HW, Sun C, et al. Interleukin-23 engineering improves CAR T cell function in solid tumors. Nat Biotechnol. 2020;38:448–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Hu W, Huang X, Huang XY, Chen WW, Hao LD, Chen ZB. Chimeric antigen receptor modified T cell (CAR-T) co-expressed with ICOSL-41BB promote CAR-T proliferation and tumor rejection. Biomed Pharmacother. 2019;118:109333.

    Article  CAS  PubMed  Google Scholar 

  83. Raulet DH. Roles of the NKG2D immunoreceptor and its ligands. Nat Rev Immunol. 2003;3:781–90.

    Article  CAS  PubMed  Google Scholar 

  84. Zhao RC, Cheng L, Jiang ZW, Wei XR, Li BH, Wu QT, et al. DNAX-activating protein 10 co-stimulation enhances the anti-tumor efficacy of chimeric antigen receptor T cells. Oncoimmunology. 2018;8:e1509173.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Siriwon N, Kim YJ, Siegler E, Chen XH, Rohrs JA, Liu YR, et al. CAR-T cells surface-engineered with drug-encapsulated nanoparticles can ameliorate intratumoral T-cell hypofunction. Cancer Immunol Res. 2018;6:812–24.

    Article  CAS  PubMed  Google Scholar 

  86. Chen Q, Hu QY, Dukhovlinova E, Chen GJ, Ahn S, Wang C, et al. Photothermal therapy promotes tumor infiltration and antitumor activity of CAR T cells. Adv Mater. 2019;31:e1900192.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Meng WCS, Pan YL, Zhao XX. Epirubicin-gold nanoparticles suppress hepatocellular carcinomaxenograft growth in nude mice. J Biomed Res 2015;29:486–90.

    PubMed Central  Google Scholar 

  88. Ma WJ, Zhu DM, Li JH, Chen X, Xie W, Jiang X, et al. Coating biomimetic nanoparticles with chimeric antigen receptor T cell-membrane provides high specificity for hepatocellular carcinoma photothermal therapy treatment. Theranostics. 2020;10:1281–95.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Hoyos V, Savoldo B, Quintarelli C, Mahendravada A, Zhang M, Vera J, et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia. 2010;24:1160–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Wang XL, Chang WC, Wong CW, Colcher D, Sherman M, Ostberg JR, et al. A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood. 2011;118:1255–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Wu CY, Roybal KT, Puchner EM, Onuffer J, Lim WA. Remote control of therapeutic T cells through a small molecule-gated chimeric receptor. Science. 2015;350:b4077.

    Article  Google Scholar 

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Acknowledgements

We thank Zhenqing Feng and Xinjian Liu (National Health Commission Key Laboratory of Antibody Techniques, Nanjing Medical University, Nanjing, China) for their revision and reading of the manuscript.

Funding

This work is supported by the National Natural Science Foundation of China (No. 81773268).

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  1. National Health Commission Key Laboratory of Antibody Techniques, Nanjing Medical University, Nanjing, 211166, China

    Jiaojiao Guo & Qi Tang

  2. Department of Pathology, Nanjing Medical University, Nanjing, 211166, China

    Jiaojiao Guo & Qi Tang

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Guo, J., Tang, Q. Recent updates on chimeric antigen receptor T cell therapy for hepatocellular carcinoma. Cancer Gene Ther 28, 1075–1087 (2021). https://doi.org/10.1038/s41417-020-00259-4

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