Volume 4, Issue 2 (Summer-Fall 2021)                   Mod Med Lab J 2021, 4(2): 19-27 | Back to browse issues page


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Shahrbaf M A, Goudarzi K, Karimi Taheri K, Keshavarz Alikhani H, Noori M. Chimeric antigen receptor (CAR) T cell therapy in hepatocellular carcinoma; a review of recent advances. Mod Med Lab J. 2021; 4 (2) :19-27
URL: http://modernmedlab.com/article-1-106-en.html
Abstract:   (323 Views)
Novel therapeutic options such as adoptive immunotherapy have been progressed drastically for treating hepatocellular carcinoma (HCC). Chimeric antigen receptor T cell (CAR-T) therapy is a kind of adoptive immunotherapy that has been associated with promising results in hematopoietic malignancies. However, its application is associated with some obstacles in solid tumors, including heterogeneity of tumor antigens, immunosuppressive microenvironment, and serious adverse complications. In recent years, some progress has been made in this regard, and several preclinical and phase I clinical trial studies have been conducted concerning the application of CAR T-cells in solid tumors. This study will review the possibilities of CAR T cell therapy in HCC, the most common primary liver cancer associated with high morbidities and mortality globally.
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Type of Study: Review | Subject: Immunology

References
1. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301-14. [DOI:10.1016/S0140-6736(18)30010-2]
2. Aly A, Ronnebaum S, Patel D, Doleh Y, Benavente F. Epidemiologic, humanistic and economic burden of hepatocellular carcinoma in the USA: a systematic literature review. Hepat Oncol. 2020;7(3):HEP27-HEP. [DOI:10.2217/hep-2020-0024]
3. Dasgupta P, Henshaw C, Youlden DR, Clark PJ, Aitken JF, Baade PD. Global Trends in Incidence Rates of Primary Adult Liver Cancers: A Systematic Review and Meta-Analysis. Front Oncol. 2020;10. [DOI:10.3389/fonc.2020.00171]
4. Hassanipour S, Vali M, Gaffari-Fam S, Nikbakht H-A, Abdzadeh E, Joukar F, et al. The survival rate of hepatocellular carcinoma in Asian countries: a systematic review and meta-analysis. EXCLI J. 2020;19:108-30. [DOI:10.17179/excli2019-1842]
5. Childs A, O’Beirne J, Meyer T. Status of hepatocellular cancer in Europe. Chinese Clinical Oncology. 2013;2(4):14. [DOI:10.3978/j.issn.2304-3865.2013.09.04]
6. Raza A, Sood GK. Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J Gastroenterol. 2014;20(15):4115-27. [DOI:10.3748/wjg.v20.i15.4115]
7. Tan S, Li D, Zhu X. Cancer immunotherapy: Pros, cons and beyond. Biomed Pharmacother. 2020;124:109821. [DOI:10.1016/j.biopha.2020.109821]
8. Barrett DM, Grupp SA, June CH. Chimeric Antigen Receptor- and TCR-Modified T Cells Enter Main Street and Wall Street. J Immunol. 2015;195(3):755-61. [DOI:10.4049/jimmunol.1500751]
9. Hulen TM, Chamberlain CA, Svane IM, Met Ö. ACT Up TIL Now: The Evolution of Tumor-Infiltrating Lymphocytes in Adoptive Cell Therapy for the Treatment of Solid Tumors. Immuno. 2021;1(3):194-211. [DOI:10.3390/immuno1030012]
10. Tsimberidou AM, Van Morris K, Vo HH, Eck S, Lin YF, Rivas JM, et al. T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors. J Hematol Oncol. 2021;14(1):102. [DOI:10.1186/s13045-021-01115-0]
11. Zhao L, Cao YJ. Engineered T Cell Therapy for Cancer in the Clinic. Front Immunol. 2019;10:2250. [DOI:10.3389/fimmu.2019.02250]
12. Morotti M, Albukhari A, Alsaadi A, Artibani M, Brenton JD, Curbishley SM, et al. Promises and challenges of adoptive T-cell therapies for solid tumours. Br J Cancer. 2021;124(11):1759-76. [DOI:10.1038/s41416-021-01353-6]
13. Kirtane K, Elmariah H, Chung CH, Abate-Daga D. Adoptive cellular therapy in solid tumor malignancies: review of the literature and challenges ahead. J Immunother Cancer. 2021;9(7). [DOI:10.1136/jitc-2021-002723]
14. Hou AJ, Chen LC, Chen YY. Navigating CAR-T cells through the solid-tumour microenvironment. Nat Rev Drug Discov. 2021;20(7):531-50. [DOI:10.1038/s41573-021-00189-2]
15. Yeku O, Li X, Brentjens RJ. Adoptive T-Cell Therapy for Solid Tumors. Am Soc Clin Oncol Educ Book. 2017;37:193-204. [DOI:10.1200/EDBK_180328]
16. Zhao Z, Chen Y, Francisco NM, Zhang Y, Wu M. The application of CAR-T cell therapy in hematological malignancies: advantages and challenges. Acta Pharm Sin B. 2018;8(4):539-51. [DOI:10.1016/j.apsb.2018.03.001]
17. Subklewe M, von Bergwelt-Baildon M, Humpe A. Chimeric Antigen Receptor T Cells: A Race to Revolutionize Cancer Therapy. Transfus Med Hemother. 2019;46(1):15-24. [DOI:10.1159/000496870]
18. Benmebarek M-R, Karches CH, Cadilha BL, Lesch S, Endres S, Kobold S. Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells. Int J Mol Sci. 2019;20(6):1283. [DOI:10.3390/ijms20061283]
19. Lukjanov V, Koutná I, Šimara P. CAR T-Cell Production Using Nonviral Approaches. J Immunol Res. 2021;2021:6644685-. [DOI:10.1155/2021/6644685]
20. Abou-El-Enein M, Elsallab M, Feldman SA, Fesnak AD, Heslop HE, Marks P, et al. Scalable Manufacturing of CAR T cells for Cancer Immunotherapy. Blood Cancer Discov. 2021;2(5):408-22. [DOI:10.1158/2643-3230.BCD-21-0084]
21. Zhang C, Liu J, Zhong JF, Zhang X. Engineering CAR-T cells. Biomark Res. 2017;5:22. [Google Scholar]
22. Albinger N, Hartmann J, Ullrich E. Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany. Gene Ther. 2021;28(9):513-27. [DOI:10.1038/s41434-021-00246-w]
23. Edeline J, Houot R, Marabelle A, Alcantara M. CAR-T cells and BiTEs in solid tumors: challenges and perspectives. J Hematol Oncol. 2021;14(1):65. [DOI:10.1186/s13045-021-01067-5]
24. Marofi F, Motavalli R, Safonov VA, Thangavelu L, Yumashev AV, Alexander M, et al. CAR T cells in solid tumors: challenges and opportunities. Stem Cell Res Ther. 2021;12(1):81. [DOI:10.1186/s13287-020-02128-1]
25. Sharma S. Tumor markers in clinical practice: General principles and guidelines. Indian J Med Paediatr Oncol. 2009;30(1):1-8. [DOI:10.4103/0971-5851.56328]
26. Vaidyanathan K, Vasudevan DM. Organ Specific Tumor Markers: What's New? Indian J Clin Biochem. 2012;27(2):110-20. [DOI:10.1007/s12291-011-0173-8]
27. The Lancet O. CAR T-cell therapy for solid tumours. Lancet Oncol. 2021;22(7):893. [DOI:10.1016/S1470-2045(21)00353-3]
28. Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 2010;18(4):843-51. [DOI:10.1038/mt.2010.24]
29. Lamers CH, Sleijfer S, van Steenbergen S, van Elzakker P, van Krimpen B, Groot C, et al. Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Mol Ther. 2013;21(4):904-12. [DOI:10.1038/mt.2013.17]
30. Jayaraman J, Mellody MP, Hou AJ, Desai RP, Fung AW, Pham AHT, et al. CAR-T design: Elements and their synergistic function. EBioMedicine. 2020;58:102931. [DOI:10.1016/j.ebiom.2020.102931]
31. Majzner RG, Mackall CL. Tumor Antigen Escape from CAR T-cell Therapy. Cancer Discov. 2018;8(10):1219-26. [DOI:10.1158/2159-8290.CD-18-0442]
32. D'Aloia MM, Zizzari IG, Sacchetti B, Pierelli L, Alimandi M. CAR-T cells: the long and winding road to solid tumors. Cell Death Dis. 2018;9(3):282. [DOI:10.1038/s41419-018-0278-6]
33. Salmon H, Franciszkiewicz K, Damotte D, Dieu-Nosjean MC, Validire P, Trautmann A, et al. Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J Clin Invest. 2012;122(3):899-910. [DOI:10.1172/JCI45817]
34. Murad JP, Kozlowska AK, Lee HJ, Ramamurthy M, Chang WC, Yazaki P, et al. Effective Targeting of TAG72(+) Peritoneal Ovarian Tumors via Regional Delivery of CAR-Engineered T Cells. Front Immunol. 2018;9:2268. [DOI:10.3389/fimmu.2018.02268]
35. Zuo BL, Yan B, Zheng GX, Xi WJ, Zhang X, Yang AG, et al. Targeting and suppression of HER3-positive breast cancer by T lymphocytes expressing a heregulin chimeric antigen receptor. Cancer Immunol Immunother. 2018;67(3):393-401. [DOI:10.1007/s00262-017-2089-5]
36. Junghans RP, Ma Q, Rathore R, Gomes EM, Bais AJ, Lo AS, et al. Phase I Trial of Anti-PSMA Designer CAR-T Cells in Prostate Cancer: Possible Role for Interacting Interleukin 2-T Cell Pharmacodynamics as a Determinant of Clinical Response. Prostate. 2016;76(14):1257-70. [DOI:10.1002/pros.23214]
37. Zhao W, Jia L, Zhang M, Huang X, 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(8):1846-56. [Article]
38. Deng X, Gao F, Li N, Li Q, Zhou Y, Yang T, et al. Antitumor activity of NKG2D CAR-T cells against human colorectal cancer cells in vitro and in vivo. Am J Cancer Res. 2019;9(5):945-58. [Article]
39. Koulouris A, Tsagkaris C, Spyrou V, Pappa E, Troullinou A, Nikolaou M. Hepatocellular Carcinoma: An Overview of the Changing Landscape of Treatment Options. J Hepatocell Carcinoma. 2021;8:387-401. [DOI:10.2147/JHC.S300182]
40. Görög D, Regöly-Mérei J, Paku S, Kopper L, Nagy P. Alpha-fetoprotein expression is a potential prognostic marker in hepatocellular carcinoma. World J Gastroenterol. 2005;11(32):5015-8. [DOI:10.3748/wjg.v11.i32.5015]
41. Kandasamy A, Pottakkat B. Alpha-fetoprotein: A molecular bootstrap for hepatocellular carcinoma. International Journal of Molecular & Immuno Oncology. 2020;5(3):92-5. [DOI:10.25259/IJMIO_5_2020]
42. Liu H, Xu Y, Xiang J, Long L, Green S, Yang Z, et al. Targeting Alpha-Fetoprotein (AFP)-MHC Complex with CAR T-Cell Therapy for Liver Cancer. Clin Cancer Res. 2017;23(2):478-88. [DOI:10.1158/1078-0432.CCR-16-1203]
43. Zhou F, Shang W, Yu X, Tian J. Glypican-3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment. Med Res Rev. 2018;38(2):741-67. [DOI:10.1002/med.21455]
44. Rochigneux P, Chanez B, De Rauglaudre B, Mitry E, Chabannon C, Gilabert M. Adoptive Cell Therapy in Hepatocellular Carcinoma: Biological Rationale and First Results in Early Phase Clinical Trials. Cancers (Basel). 2021;13(2):271. [DOI:10.3390/cancers13020271]
45. Wu Y, Liu H, Ding H. GPC-3 in hepatocellular carcinoma: current perspectives. Journal of hepatocellular carcinoma. 2016;3:63-7. [DOI:10.2147/JHC.S116513]
46. Shimizu Y, Suzuki T, Yoshikawa T, Endo I, Nakatsura T. Next-Generation Cancer Immunotherapy Targeting Glypican-3. Front Oncol. 2019;9:248. [DOI:10.3389/fonc.2019.00248]
47. Gao W, Ho M. The role of glypican-3 in regulating Wnt in hepatocellular carcinomas. Cancer Rep. 2011;1(1):14-9. [Article]
48. Gao H, Li K, Tu H, Pan X, Jiang H, Shi B, et al. Development of T cells redirected to glypican-3 for the treatment of hepatocellular carcinoma. Clin Cancer Res. 2014;20(24):6418-28. [DOI:10.1158/1078-0432.CCR-14-1170]
49. Jiang Z, Jiang X, Chen S, Lai Y, Wei X, Li B, 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. [DOI:10.3389/fimmu.2016.00690]
50. Liu X, Wen J, Yi H, Hou X, Yin Y, Ye G, et al. Split chimeric antigen receptor-modified T cells targeting glypican-3 suppress hepatocellular carcinoma growth with reduced cytokine release. Ther Adv Med Oncol. 2020;12:1758835920910347. [DOI:10.1177/1758835920910347]
51. Landras A, Reger de Moura C, Jouenne F, Lebbe C, Menashi S, Mourah S. CD147 Is a Promising Target of Tumor Progression and a Prognostic Biomarker. Cancers (Basel). 2019;11(11):1803. [DOI:10.3390/cancers11111803]
52. Wang SJ, Chao D, Wei W, Nan G, Li JY, Liu FL, et al. CD147 promotes collective invasion through cathepsin B in hepatocellular carcinoma. J Exp Clin Cancer Res. 2020;39(1):145. [DOI:10.1186/s13046-020-01647-2]
53. 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. [DOI:10.3389/fcell.2019.00233]
54. Tseng H-c, Xiong W, Badeti S, Yang Y, Ma M, Liu T, et al. Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma. Nature Communications. 2020;11(1):4810. [DOI:10.1038/s41467-020-18444-2]
55. Yi F-T, Lu Q-P. Mucin 1 promotes radioresistance in hepatocellular carcinoma cells through activation of JAK2/STAT3 signaling. Oncol Lett. 2017;14(6):7571-6. [DOI:10.3892/ol.2017.7119]
56. Ma Y, Wang Z, Gong R, Li L, Wu H, Jin H. Specific cytotoxicity of MUC1 chimeric antigen receptor-engineered Jurkat T cells against hepatocellular carcinoma. Acad J Second Mil Med Univ. 2014;5:1177-82. [DOI:10.3724/SP.J.1008.2014.01177]
57. Trzpis M, McLaughlin PMJ, de Leij LMFH, Harmsen MC. Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule. Am J Pathol. 2007;171(2):386-95. [DOI:10.2353/ajpath.2007.070152]
58. Zhou Y, Wen P, Li M, Li Y, Li XA. Construction of chimeric antigen receptor‑modified T cells targeting EpCAM and assessment of their anti‑tumor effect on cancer cells. Mol Med Rep. 2019;20(3):2355-64. [DOI:10.3892/mmr.2019.10460]
59. Fu J, Shang Y, Qian Z, Hou J, Yan F, Liu G, et al. Chimeric Antigen receptor-T (CAR-T) cells targeting Epithelial cell adhesion molecule (EpCAM) can inhibit tumor growth in ovarian cancer mouse model. J Vet Med Sci. 2021;83(2):241-7. [DOI:10.3892/mmr.2019.10460]
60. Wang H, Rao B, Lou J, Li J, Liu Z, Li A, et al. The Function of the HGF/c-Met Axis in Hepatocellular Carcinoma. Frontiers in Cell and Developmental Biology. 2020;8. [DOI:10.3389/fcell.2020.00055]
61. Jiang W, Li T, Guo J, Wang J, Jia L, Shi X, et al. Bispecific c-Met/PD-L1 CAR-T Cells Have Enhanced Therapeutic Effects on Hepatocellular Carcinoma. Front Oncol. 2021;11:546586. [DOI:10.3389/fonc.2021.546586]
62. Carapito R, Aouadi I, Ilias W, Bahram S. Natural Killer Group 2, Member D/NKG2D Ligands in Hematopoietic Cell Transplantation. Frontiers in immunology. 2017;8:368. [DOI:10.3389/fimmu.2017.00368]
63. Tsukagoshi M, Wada S, Yokobori T, Altan B, Ishii N, Watanabe A, et al. Overexpression of natural killer group 2 member D ligands predicts favorable prognosis in cholangiocarcinoma. Cancer Science. 2016;107(2):116-22. [DOI:10.1111/cas.12853]
64. Zhu H, Wang B, Kong L, An T, Li G, Zhou H, et al. Parvifoline AA Promotes Susceptibility of Hepatocarcinoma to Natural Killer Cell-Mediated Cytolysis by Targeting Peroxiredoxin. Cell Chemical Biology. 2019;26(8):1122-32.e6. [DOI:10.1016/j.chembiol.2019.04.003]
65. Sun B, Yang D, Dai H, Liu X, Jia R, Cui X, et al. Eradication of Hepatocellular Carcinoma by NKG2D-Based CAR-T Cells. Cancer Immunol Res. 2019;7(11):1813-23. [DOI:10.1158/2326-6066.CIR-19-0026]
66. Barzegar Behrooz A, Syahir A, Ahmad S. CD133: beyond a cancer stem cell biomarker. J Drug Target. 2019;27(3):257-69. [DOI:10.1080/1061186X.2018.1479756]
67. Liu F, Qian Y. The role of CD133 in hepatocellular carcinoma. Cancer Biol Ther. 2021;22(4):291-300. [DOI:10.1080/15384047.2021.1916381]
68. Wang Y, Chen M, Wu Z, Tong C, Dai H, Guo Y, et al. CD133-directed CAR T cells for advanced metastasis malignancies: A phase I trial. Oncoimmunology. 2018;7(7):e1440169. [DOI:10.1080/2162402X.2018.1440169]
69. Dai H, Tong C, Shi D, Chen M, Guo Y, Chen D, et al. Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: a single-arm, open-label, phase II trial. Oncoimmunology. 2020;9(1):1846926. [DOI:10.1080/2162402X.2020.1846926]

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