Clinical Study on the Efficacy and Safety of c-Met/PD-L1 CAR-T Cell Injection in the Treatment of HCC

Summary

Title: Single-center, open clinical study on the efficacy and safety of c-Met/PD-L1 T cell injection in the treatment of primary hepatocellular carcinoma Stage: Phase I clinical trial Purpose: To evaluate the efficacy and safety of c-Met/PD-L1 CAR-T cells in patients with primary hepatocellular carcinoma Object: patients with primary hepatocellular carcinoma Sample size: 50 cases Number of centres：1 Study design: CT, MRI, PET and blood biochemical tests were performed before treatment to evaluate the state of HCC. Peripheral blood of the patient was extracted and PBMC was isolated. CAR-T cells were obtained by tranducing PBMC with c-Met/PD-L1 CAR lentivirus, and the proliferation capacity and immune phenotype of the cells were tested. After passing the inspection, the cells were re-injected into the patient three times. The efficacy and safety of c-Met/PD-L1 CAR-T cells was assessed respectively at 4 week, 12 week, 24 week and 48 week after treatment. Trial product: c-Met/PD-L1 CAR-T cells Course of treatment: 3 days for a course of treatment, only one course of treatment. A second course is given as appropriate if the treatment is beneficial to the patient.

Timeline

Start

2018-10-01

Primary completion

2019-10-30

Completion

2019-10-30

Publications

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• Background McGlynn KA, Petrick JL, London WT. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis. 2015 May;19(2):223-38. doi: 10.1016/j.cld.2015.01.001. Epub 2015 Feb 26.
• Background Tagliamonte M, Petrizzo A, Tornesello ML, Ciliberto G, Buonaguro FM, Buonaguro L. Combinatorial immunotherapy strategies for hepatocellular carcinoma. Curr Opin Immunol. 2016 Apr;39:103-13. doi: 10.1016/j.coi.2016.01.005. Epub 2016 Feb 4.
• Background Kenderian SS, Ruella M, Gill S, Kalos M. Chimeric antigen receptor T-cell therapy to target hematologic malignancies. Cancer Res. 2014 Nov 15;74(22):6383-9. doi: 10.1158/0008-5472.CAN-14-1530. Epub 2014 Nov 4.
• Background Pico de Coana Y, Choudhury A, Kiessling R. Checkpoint blockade for cancer therapy: revitalizing a suppressed immune system. Trends Mol Med. 2015 Aug;21(8):482-91. doi: 10.1016/j.molmed.2015.05.005. Epub 2015 Jun 16.
• Background Brentjens RJ, Riviere I, Park JH, Davila ML, Wang X, Stefanski J, Taylor C, Yeh R, Bartido S, Borquez-Ojeda O, Olszewska M, Bernal Y, Pegram H, Przybylowski M, Hollyman D, Usachenko Y, Pirraglia D, Hosey J, Santos E, Halton E, Maslak P, Scheinberg D, Jurcic J, Heaney M, Heller G, Frattini M, Sadelain M. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. 2011 Nov 3;118(18):4817-28. doi: 10.1182/blood-2011-04-348540. Epub 2011 Aug 17.
• Background Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235-71. doi: 10.1146/annurev-immunol-031210-101324.
• Background Dotti G, Savoldo B, Brenner M. Fifteen years of gene therapy based on chimeric antigen receptors: "are we nearly there yet?". Hum Gene Ther. 2009 Nov;20(11):1229-39. doi: 10.1089/hum.2009.142.
• Background Park TS, Rosenberg SA, Morgan RA. Treating cancer with genetically engineered T cells. Trends Biotechnol. 2011 Nov;29(11):550-7. doi: 10.1016/j.tibtech.2011.04.009. Epub 2011 Jun 12.
• Background Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I, Stetler-Stevenson M, Phan GQ, Hughes MS, Sherry RM, Yang JC, Kammula US, Devillier L, Carpenter R, Nathan DA, Morgan RA, Laurencot C, Rosenberg SA. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood. 2012 Mar 22;119(12):2709-20. doi: 10.1182/blood-2011-10-384388. Epub 2011 Dec 8.
• Background Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, Chung SS, Stefanski J, Borquez-Ojeda O, Olszewska M, Qu J, Wasielewska T, He Q, Fink M, Shinglot H, Youssif M, Satter M, Wang Y, Hosey J, Quintanilla H, Halton E, Bernal Y, Bouhassira DC, Arcila ME, Gonen M, Roboz GJ, Maslak P, Douer D, Frattini MG, Giralt S, Sadelain M, Brentjens R. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014 Feb 19;6(224):224ra25. doi: 10.1126/scitranslmed.3008226.
• Background 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 Jul 10;124(2):188-95. doi: 10.1182/blood-2014-05-552729. Epub 2014 May 29.
• Background Maus MV, Grupp SA, Porter DL, June CH. Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood. 2014 Apr 24;123(17):2625-35. doi: 10.1182/blood-2013-11-492231. Epub 2014 Feb 27.
• Background Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J. 2014 Mar-Apr;20(2):119-22. doi: 10.1097/PPO.0000000000000035.
• Background Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
• Background Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016 Jun 30;127(26):3321-30. doi: 10.1182/blood-2016-04-703751. Epub 2016 May 20.

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