Abstract
Our previous work involved the development of a recombinant fowlpox virus encoding survivin (FP-surv) vaccine that was evaluated for efficacy in mesothelioma mouse models. Results showed that FP-surv vaccination generated significant immune responses, which led to delayed tumor growth and improved animal survival. We have extended those previous findings in the current study, which involves the pre-clinical development of an optimized version of FP-surv designed for human immunization (HIvax). Survivin-derived peptides for the most common haplotypes in the human population were identified and their immunogenicity confirmed in co-culture experiments using dendritic cells and T cells isolated from healthy donors. Peptides confirmed to induce CD8+ and CD4+ T cells activation in humans were then included in 2 transgenes optimized for presentation of processed peptides on MHC-I (HIvax1) and MHC-II (HIvax2). Fowlpox vectors expressing the HIvax transgenes were then generated and their efficacy was evaluated with subsequent co-culture experiments to measure interferon-γ and granzyme B secretion. In these experiments, both antigen specific CD4+ and CD8+ T cells were activated by HIvax vaccines with resultant cytotoxic activity against survivin-overexpressing mesothelioma cancer cells. These results provide a rationale for clinical testing of HIvax1 and HIvax2 vaccines in patients with survivin-expressing cancers.
Original language | English |
---|---|
Pages (from-to) | 1585-1595 |
Number of pages | 11 |
Journal | Human Vaccines and Immunotherapeutics |
Volume | 11 |
Issue number | 7 |
DOIs | |
Publication status | Published - Jan 1 2015 |
Keywords
- Cancer vaccines
- EpiMatrix
- Fowlpox
- Immunodominant epitopes
- Mesothelioma
- T-Lymphocytes
- Tregitopes
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Pharmacology