Luis Teixeira 1 , Jacques Medioni 2 , Julie Garibal 3 , Olivier Adotevi 4 , Ludovic Doucet 1 , Marie-Agnès Dragon Durey 5 , Zineb Ghrieb 1 , Jean-Jacques Kiladjian 1 , Mara Brizard 2 , Caroline Laheurte 4 , Maria Wehbe 6 , Elodie Pliquet 6 , Marie Escande 6 , Rémy Defrance 6 , Stephane Culine 1 , Stephane Oudard 2 , Simon Wain-Hobson 6 , Valérie Doppler 6 , Thierry Huet 6 , Pierre Langlade-Demoyen 6 Show Affiliations »
Abstract
PURPOSE: Human telomerase reverse transcriptase (hTERT) is highly expressed in >85% of human tumors and is thus considered as a good tumor-associated antigen candidate for vaccine development. We conducted a phase I study to investigate the safety, tolerability, clinical response, and immunogenicity of INVAC-1, a DNA plasmid encoding a modified hTERT protein in patients with relapsed or refractory solid tumors. PATIENTS AND METHODS: INVAC-1 was either administered by intradermal route followed by electroporation or by Tropis, a needle-free injection system. Safety and tolerability were monitored by clinical and laboratory assessments. Progression-free survival and overall survival were reported using Kaplan-Meier survival analysis. Immunogenicity was studied by ELISpot, Luminex, and Flow Cytometry. RESULTS: Twenty-six patients were treated with INVAC-1 administered at three dose levels (100, 400, and 800 μg). Vaccination was well tolerated and no dose-limiting toxicity was reported. One treatment-related grade 3 SAE was reported. Fifty-eight percent of patients experienced disease stabilization. PFS was 2.7 months, median OS was 15 months, and 1-year survival was reached for 65% of patients. INVAC-1 vaccination stimulated specific anti-hTERT CD4 T-cell response as well as cytotoxic CD8 T-cell response. No evidence of peripheral vaccine-induced immunosuppression was observed. CONCLUSIONS: INVAC-1 vaccination was safe, well tolerated, and immunogenic when administered intradermally at the three tested doses in patients with relapsed or refractory cancers. Disease stabilization was observed for the majority of patients (58%) during the treatment period and beyond. ©2019 American Association for Cancer Research.
PURPOSE: Human telomerase reverse transcriptase (hTERT ) is highly expressed in >85% of human tumors and is thus considered as a good tumor -associated antigen candidate for vaccine development. We conducted a phase I study to investigate the safety, tolerability, clinical response, and immunogenicity of INVAC-1, a DNA plasmid encoding a modified hTERT protein in patients with relapsed or refractory solid tumors . PATIENTS AND METHODS: INVAC-1 was either administered by intradermal route followed by electroporation or by Tropis, a needle-free injection system. Safety and tolerability were monitored by clinical and laboratory assessments. Progression-free survival and overall survival were reported using Kaplan-Meier survival analysis. Immunogenicity was studied by ELISpot, Luminex, and Flow Cytometry. RESULTS: Twenty-six patients were treated with INVAC-1 administered at three dose levels (100, 400, and 800 μg). Vaccination was well tolerated and no dose-limiting toxicity was reported. One treatment-related grade 3 SAE was reported. Fifty-eight percent of patients experienced disease stabilization. PFS was 2.7 months, median OS was 15 months, and 1-year survival was reached for 65% of patients . INVAC-1 vaccination stimulated specific anti-hTERT CD4 T-cell response as well as cytotoxic CD8 T-cell response. No evidence of peripheral vaccine-induced immunosuppression was observed. CONCLUSIONS: INVAC-1 vaccination was safe, well tolerated, and immunogenic when administered intradermally at the three tested doses in patients with relapsed or refractory cancers . Disease stabilization was observed for the majority of patients (58%) during the treatment period and beyond. ©2019 American Association for Cancer Research.
Entities: Disease
Gene
Species
Year: 2019
PMID： 31558479 DOI： 10.1158/1078-0432.CCR-19-1614
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531