Preclinical Development of TVAX: An Advanced Multiantigen Vaccine for Therapy and Prevention of Malignant Mesothelioma
Abstract
We proposed to evaluate the efficacy of multi-antigen vaccines for the treatment of malignant mesothelioma (MM) in mice. In the 1st year of this projects, we developed different immunotherapies using viral vector-based vaccines as MVA or Fowlpox, as well as peptide-based vaccines. For the first prototypes of these vaccines, Tvax and Tvax 2.0, we have included antigens previously demonstrated to be highly expressed in human tumors. Unexpectedly, these vaccines resulted ineffective in reducing MM in mice and displayed signs of autoimmunity. We hypothesized that these negative results were caused by a reduced expression in mouse MM of the antigens included in Tvax vaccines. A whole transcriptome analysis to compare antigen expression between MM and normal tissues confirmed our assumption. This analysis also allowed us to choose a new set of antigens that presented more effective anti-cancer responses in our experiments, without generating auto-immunity. During the 2nd year of this project, we focused in evaluating the anti-cancer efficacy of Tvax 3.0 vaccines, which include this new set of antigens. We also characterized the antigen-specific immune responses generated by Tvax 3.0 and analyzed immune cell infiltrates in tumors from vaccinated mice. All these data were incorporated in a manuscript that will be submitted for publication in the following weeks.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2018
- Accession Number
- AD1060916
Entities
People
- Pietro Bertino
Organizations
- University of Hawaiʻi System