Preclinical Development of TVAX: An Advanced Multiantigen Vaccine for Therapy and Prevention of Malignant Mesothelioma
Technical Report,15 Aug 2016,14 Aug 2017
Unviersity of Hawaii Honolulu United States
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We proposed to evaluate the efficacy of a multi-antigen vaccine for the treatment of malignant mesothelioma MM in mice. The first version of this vaccine, called mTvax, included epitopes to activate antigen-specific T cells against survivin, metastasin, midkine, Wilms Tumor 1, brachyury, Fibroblast Activation Protein and VEGFR2. In mTvax we also included the immunostimulatory molecules CD80, CD54, and CD48 with the purpose of improving T cells responses. The mTvax antigen, comprising of the epitopes for T cell activation and the three immunostimulatory molecules, has been inserted into the DNA of different vectors p-mTvax, MVA-mTvax and FP-mTvax. When experiments were performed to evaluate the efficacy of mTvax vaccines, only FP-mTvax induced a statistically significant delay in tumor progression. Moreover, when we combined FP-mTvax with OX40 agonist antibodies OX86, we did not observe any reduction in tumor growth. To investigate our hypothesis that CD80, CD54, and CD48 reduce the efficacy of our vaccines, we produced mTvax 2.0 that expresses the same cancer antigen of mTvax but lacks the three immune stimulatory molecules. Experiments performed using mTvax 2.0 in mice carrying MM tumors showed vaccine-induced specific T cell responses and delay in tumor growth using both MVA and FP vectors.
- Medicine and Medical Research