Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: a single-arm, open-label, phase II trial

References

• F. Bray, J. Ferlay, I. Soerjomataram, R.L. Siegel, L.A. Torre, A. Jemal. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–8. doi:10.3322/caac.21492.
   PubMed Web of Science ®Google Scholar
• European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–943. doi:10.1016/j.jhep.2011.12.001.
   PubMed Web of Science ®Google Scholar
• G.K. Abou-Alfa, T. Meyer, A.L. Cheng, A.B. El-Khoueiry, L. Rimassa, B.Y. Ryoo, I. Cicin, P. Merle, Y. Chen, J.W. Park, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63. doi:10.1056/NEJMoa1717002.
   PubMed Web of Science ®Google Scholar
• J.M. Llovet, S. Ricci, V. Mazzaferro, P. Hilgard, E. Gane, J.F. Blanc, A.C. de Oliveira, A. Santoro, J.L. Raoul, A. Forner, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–390. doi:10.1056/NEJMoa0708857.
   PubMed Web of Science ®Google Scholar
• M. Kudo, R.S. Finn, S. Qin, K.H. Han, K. Ikeda, F. Piscaglia, A. Baron, J.W. Park, G. Han, J. Jassem, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163–1173. doi:10.1016/S0140-6736(18)30207-1.
   PubMed Web of Science ®Google Scholar
• J. Bruix, S. Qin, P. Merle, A. Granito, Y.H. Huang, G. Bodoky, M. Pracht, O. Yokosuka, O. Rosmorduc, V. Breder, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389(10064):56–66. doi:10.1016/S0140-6736(16)32453-9.
   PubMed Web of Science ®Google Scholar
• A.B. El-Khoueiry, B. Sangro, T. Yau, T.S. Crocenzi, M. Kudo, C. Hsu, T.Y. Kim, S.P. Choo, J. Trojan, T.H.R. Welling, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389(10088):2492–2502. doi:10.1016/S0140-6736(17)31046-2.
   PubMed Web of Science ®Google Scholar
• de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6(1):24–37. doi:10.1038/nrc1782.
   PubMed Web of Science ®Google Scholar
• Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer. 2008;8:618–631.
   PubMed Web of Science ®Google Scholar
• De Palma M, Venneri MA, Roca C, Naldini L. Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells. Nat Med. 2003;9(6):789–795. doi:10.1038/nm871.
   PubMed Web of Science ®Google Scholar
• F. Shojaei, X. Wu, A.K. Malik, C. Zhong, M.E. Baldwin, S. Schanz, G. Fuh, H.P. Gerber, N. Ferrara. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol. 2007;25(8):911–920. doi:10.1038/nbt1323.
   PubMed Web of Science ®Google Scholar
• Ribatti D. The involvement of endothelial progenitor cells in tumor angiogenesis. J Cell Mol Med. 2004;8(3):294–300. doi:10.1111/j.1582-4934.2004.tb00319.x.
   PubMed Web of Science ®Google Scholar
• J.W. Ho, R.W. Pang, C. Lau, C.K. Sun, W.C. Yu, S.T. Fan, R.T. Poon. Significance of circulating endothelial progenitor cells in hepatocellular carcinoma. Hepatology. 2006;44(4):836–843. doi:10.1002/hep.21353.
   PubMed Web of Science ®Google Scholar
• D. Gao, D.J. Nolan, A.S. Mellick, K. Bambino, K. McDonnell, V. Mittal. Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science. 2008;319(5860):195–198. doi:10.1126/science.1150224.
   PubMed Web of Science ®Google Scholar
• Y. Shaked, E. Henke, J.M. Roodhart, P. Mancuso, M.H. Langenberg, M. Colleoni, L.G. Daenen, S. Man, P. Xu, U. Emmenegger, T. Tang, et al. Rapid chemotherapy-induced acute endothelial progenitor cell mobilization: implications for antiangiogenic drugs as chemosensitizing agents. Cancer Cell. 2008;14(3):263–273. doi:10.1016/j.ccr.2008.08.001.
   PubMed Web of Science ®Google Scholar
• D. Yu, X. Sun, Y. Qiu, J. Zhou, Y. Wu, L. Zhuang, J. Chen, Y. Ding. Identification and clinical significance of mobilized endothelial progenitor cells in tumor vasculogenesis of hepatocellular carcinoma. Clin Cancer Res. 2007;13(13):3814–3824. doi:10.1158/1078-0432.CCR-06-2594.
   PubMed Web of Science ®Google Scholar
• X.T. Sun, X.W. Yuan, H.T. Zhu, Z.M. Deng, D.C. Yu, X. Zhou, Y.T. Ding. Endothelial precursor cells promote angiogenesis in hepatocellular carcinoma. World J Gastroenterol. 2012;18(35):4925–4933. doi:10.3748/wjg.v18.i35.4925.
   PubMed Web of Science ®Google Scholar
• W. Song, H. Li, K. Tao, R. Li, Z. Song, Q. Zhao, F. Zhang, K. Dou. Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma. Int J Clin Pract. 2008;62(8):1212–1218. doi:10.1111/j.1742-1241.2008.01777.x.
   PubMed Web of Science ®Google Scholar
• C. Won, B.H. Kim, E.H. Yi, K.J. Choi, E.K. Kim, J.M. Jeong, J.H. Lee, J.J. Jang, J.H. Yoon, W.I. Jeong, et al. Signal transducer and activator of transcription 3-mediated CD133 up-regulation contributes to promotion of hepatocellular carcinoma. Hepatology. 2015;62(4):1160–1173. doi:10.1002/hep.27968.
   PubMed Web of Science ®Google Scholar
• L.M. Smith, A. Nesterova, M.C. Ryan, S. Duniho, M. Jonas, M. Anderson, R.F. Zabinski, M.K. Sutherland, H.P. Gerber, K.L. Van Orden, et al. CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. Br J Cancer. 2008;99(1):100–109. doi:10.1038/sj.bjc.6604437.
   PubMed Web of Science ®Google Scholar
• K. Kohga, T. Tatsumi, T. Takehara, H. Tsunematsu, S. Shimizu, M. Yamamoto, A. Sasakawa, T. Miyagi, N. Hayashi. Expression of CD133 confers malignant potential by regulating metalloproteinases in human hepatocellular carcinoma. J Hepatol. 2010;52(6):872–879. doi:10.1016/j.jhep.2009.12.030.
   PubMed Web of Science ®Google Scholar
•  X.R. Yang, Y. Xu, B. Yu, J. Zhou, S.J. Qiu, G.M. Shi, B.H. Zhang, W.Z. Wu, Y.H. Shi, B. Wu, G.H. Yang, et al. High expression levels of putative hepatic stem/progenitor cell biomarkers related to tumour angiogenesis and poor prognosis of hepatocellular carcinoma. Gut. 2010;59(7):953–962. doi:10.1136/gut.2008.176271.
   PubMed Web of Science ®Google Scholar
• Hristov M, Weber C. Endothelial progenitor cells: characterization, pathophysiology, and possible clinical relevance. J Cell Mol Med. 2004;8(4):498–508. doi:10.1111/j.1582-4934.2004.tb00474.x.
   PubMed Web of Science ®Google Scholar
• M. Peichev, A.J. Naiyer, D. Pereira, Z. Zhu, W.J. Lane, M. Williams, M.C. Oz, D.J. Hicklin, L. Witte, M.A. Moore, S. Rafii. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood. 2000;95:952–958.
   PubMed Web of Science ®Google Scholar
• Y. Duan, S. Yu, P. Xu, X. Wang, X. Feng, Z. Mao, C. Gao. Co-immobilization of CD133 antibodies, vascular endothelial growth factors, and REDV peptide promotes capture, proliferation, and differentiation of endothelial progenitor cells. Acta Biomater. 2019;96:137–148. doi:10.1016/j.actbio.2019.07.004.
   PubMed Web of Science ®Google Scholar
• Schmohl JU, Vallera DA. CD133, selectively targeting the root of cancer.
   Google Scholar
• Y. Wang, M. Chen, Z. Wu, C. Tong, H. Dai, Y. Guo, Y. Liu, J. Huang, H. Lv, C. Luo, 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.
   PubMed Web of Science ®Google Scholar
• Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188–195. doi:10.1182/blood-2014-05-552729.
   PubMed Web of Science ®Google Scholar
•  S.G. Kalathil, A.A. Lugade, R. Iyer, A. Miller, Y. Thanavala. Endothelial progenitor cell number and ERK phosphorylation serve as predictive and prognostic biomarkers in advanced hepatocellular carcinoma patients treated with sorafenib. Oncoimmunology. 2016;5(10):e1226718. doi:10.1080/2162402X.2016.1226718.
   PubMed Web of Science ®Google Scholar
• F.C. Thistlethwaite, D.E. Gilham, R.D. Guest, D.G. Rothwell, M. Pillai, D.J. Burt, A.J. Byatte, N. Kirillova, J.W. Valle, S.K. Sharma, et al. The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity. Cancer Immunol Immunother. 2017;66(11):1425–1436. doi:10.1007/s00262-017-2034-7.
   PubMed Web of Science ®Google Scholar
•  S.C. Katz, R.A. Burga, E. McCormack, L.J. Wang, W. Mooring, G.R. Point, P.D. Khare, M. Thorn, Q. Ma, B.F. Stainken, 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(14):3149–3159. doi:10.1158/1078-0432.CCR-14-1421.
   PubMed Web of Science ®Google Scholar
•  Y.T. Shih, M.C. Wang, J. Zhou, H.H. Peng, D.Y. Lee, J.J. Chiu. Endothelial progenitors promote hepatocarcinoma intrahepatic metastasis through monocyte chemotactic protein-1 induction of microRNA-21. Gut. 2015;64:1132–1147.
   PubMed Web of Science ®Google Scholar
• Ramjiawan RR, Griffioen AW, Duda DG. Anti-angiogenesis for cancer revisited: is there a role for combinations with immunotherapy? Angiogenesis. 2017;20:185–204.
   PubMed Web of Science ®Google Scholar
•  J.R. van Beijnum, P. Nowak-Sliwinska, E.J. Huijbers, V.L. Thijssen, A.W. Griffioen. The great escape; the hallmarks of resistance to antiangiogenic therapy. Pharmacol Rev. 2015;67:441–461.
   PubMed Web of Science ®Google Scholar
• Y.J. Xie, M. Dougan, N. Jailkhani, J. Ingram, T. Fang, L. Kummer, N. Momin, N. Pishesha, S. Rickelt, R.O. Hynes, H. Ploegh. Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice. Proc Natl Acad Sci U S A. 2019;116(16):7624–7631. doi:10.1073/pnas.1817147116.
   PubMed Web of Science ®Google Scholar
• Akbari P, Huijbers EJM, Themeli M, Griffioen AW, van Beijnum JR. The tumor vasculature an attractive CAR T cell target in solid tumors. Angiogenesis. 2019;22(4):473–475. doi:10.1007/s10456-019-09687-9.
   PubMed Web of Science ®Google Scholar
• D. Shi, Y. Shi, A.O. Kaseb, X. Qi, Y. Zhang, J. Chi, Q. Lu, H. Gao, H. Jiang, H. Wang, et al. Chimeric antigen receptor-glypican-3 T-Cell therapy for advanced hepatocellular carcinoma: results of phase I trials. Clin Cancer Res. 2020;26(15):3979–3989. doi:10.1158/1078-0432.CCR-19-3259.
   PubMed Web of Science ®Google Scholar
• D. Li, N. Li, Y.F. Zhang, H. Fu, M. Feng, D. Schneider, L. Su, X. Wu, J. Zhou, S. Mackay, et al. Persistent polyfunctional chimeric antigen receptor T cells that target glypican 3 eliminate orthotopic hepatocellular carcinomas in mice. Gastroenterology. 2020;158(8):2250–2265 e2220. doi:10.1053/j.gastro.2020.02.011.
   PubMed Web of Science ®Google Scholar
• Huang M, Deng J, Gao L, Zhou J. Innovative strategies to advance CAR T cell therapy for solid tumors. Am J Cancer Res. 2020;10:1979–1992.
   PubMed Web of Science ®Google Scholar
• N. Ahmed, V.S. Brawley, M. Hegde, C. Robertson, A. Ghazi, C. Gerken, E. Liu, O. Dakhova, A. Ashoori, A. Corder, et al. Human epidermal growth factor receptor 2 (her2) -specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol. 2015;33(15):1688–1696. doi:10.1200/JCO.2014.58.0225.
   PubMed Web of Science ®Google Scholar
• N. Ahmed, V. Brawley, M. Hegde, K. Bielamowicz, M. Kalra, D. Landi, C. Robertson, T.L. Gray, O. Diouf, A. Wakefield, et al. HER2-specific chimeric antigen receptor-modified virus-specific T cells for progressive glioblastoma: a phase 1 dose-escalation trial. JAMA Oncol. 2017;3(8):1094–1101. doi:10.1001/jamaoncol.2017.0184.
   PubMed Web of Science ®Google Scholar
• D.L. Porter, B.L. Levine, M. Kalos, A. Bagg and C.H. June. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365(8):725–733. doi:10.1056/NEJMoa1103849.
   PubMed Web of Science ®Google Scholar
• B. Savoldo, C.A. Ramos, E. Liu, M.P. Mims, M.J. Keating, G. Carrum, R.T. Kamble, C.M. Bollard, A.P. Gee, Z. Mei, et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest. 2011;121(5):1822–1826. doi:10.1172/JCI46110.
   PubMed Web of Science ®Google Scholar
• Weigmann A, Corbeil D, Hellwig A, Huttner WB. Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells. Proc Natl Acad Sci U S A. 1997;94(23):12425–12430. doi:10.1073/pnas.94.23.12425.
   PubMed Web of Science ®Google Scholar
• A.H. Yin, S. Miraglia, E.D. Zanjani, G. Almeida-Porada, M. Ogawa, A.G. Leary, J. Olweus, J. Kearney, D.W. Buck. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood. 1997;90(12):5002–5012. doi:10.1182/blood.V90.12.5002.
   PubMed Web of Science ®Google Scholar
• L. Mauge, A. Mejean, L. Fournier, H. Pereira, M.C. Etienne-Grimaldi, E. Levionnois, A. Caty, S. Abadie-Lacourtoisie, S. Culine, S. Le Moulec, et al. Sunitinib prior to planned nephrectomy in metastatic renal cell carcinoma: angiogenesis biomarkers predict clinical outcome in the prospective phase II PREINSUT trial. Clin Cancer Res. 2018;24(22):5534–5542. doi:10.1158/1078-0432.CCR-18-1045.
   PubMed Web of Science ®Google Scholar
• Batchelor TT, Duda DG, Di Tomaso E, et al. Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol. 2010;28(17):2817–2823. doi:10.1200/JCO.2009.26.3988.
   PubMed Web of Science ®Google Scholar
•  P. Federico, A. Petrillo, P. Giordano, D. Bosso, A. Fabbrocini, M. Ottaviano, M. Rosanova, A. Silvestri, A. Tufo, A. Cozzolino, B. Daniele. Immune checkpoint inhibitors in hepatocellular carcinoma: current status and novel perspectives. Cancers (Basel). 2020;12.
   PubMed Web of Science ®Google Scholar
• Nishida N, Kudo M. Immune checkpoint blockade for the treatment of human hepatocellular carcinoma. Hepatol Res. 2018;48(8):622–634. doi:10.1111/hepr.13191.
   PubMed Web of Science ®Google Scholar
• Yoon DH, Osborn MJ, Tolar J, Kim CJ. Incorporation of immune checkpoint blockade into chimeric antigen receptor T cells (CAR-Ts): combination or built-in CAR-T. Int J Mol Sci. 2018 Jan 24;19(2):340. doi:10.3390/ijms19020340.
   PubMed Web of Science ®Google Scholar
• Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18:197–218.
   PubMed Web of Science ®Google Scholar
• M. Hilmi, C. Neuzillet, J. Calderaro, F. Lafdil, J.M. Pawlotsky, B. Rousseau. Angiogenesis and immune checkpoint inhibitors as therapies for hepatocellular carcinoma: current knowledge and future research directions. J Immunother Cancer. 2019;7(1):333. doi:10.1186/s40425-019-0824-5.
   PubMed Web of Science ®Google Scholar