Preclinical development of HIvax: Human survivin highly immunogenic vaccines. Academic Article uri icon

Overview

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.

publication date

  • January 1, 2015

Research

keywords

  • Cancer Vaccines
  • Inhibitor of Apoptosis Proteins

Identity

PubMed Central ID

  • PMC4514257

Scopus Document Identifier

  • 84944452759

Digital Object Identifier (DOI)

  • 10.1080/21645515.2015.1050572

PubMed ID

  • 26042612

Additional Document Info

volume

  • 11

issue

  • 7