Preclinical Development of TVAX: An Advanced Multiantigen Vaccine for Therapy and Prevention of Malignant Mesothelioma
Technical Report,15 Aug 2018,14 Aug 2019
University of Hawaii Honolulu United States
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In the 1st year of this projects, we developed different immunotherapies using viral vector-based vaccines, 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 was submitted for publication at the begin of the 3rd year of this project. During the 3rd year, we performed all the experiments requested by the reviewers and successfully published an article in Frontiers in Oncology.
- Medicine and Medical Research