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Published on: January 20, 2019
Establishing the pig as a large animal model for vaccine development against human cancer
Nana H Overgaard1, Thomas M Frøsig1, Simon Welner1
1Department of Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark Copenhagen, Denmark.
Abstract:
Immunotherapy has increased overall survival of metastatic cancer patients, and cancer antigens are promising vaccine targets. To fulfill the promise, appropriate tailoring of the vaccine formulations to mount in vivo cytotoxic T cell (CTL) responses toward co-delivered cancer antigens is essential. Previous development of therapeutic cancer vaccines has largely been based on studies in mice, and the majority of these candidate vaccines failed to induce therapeutic responses in the subsequent human clinical trials. Given that antigen dose and vaccine volume in pigs are translatable to humans and the porcine immunome is closer related to the human counterpart, we here introduce pigs as a supplementary large animal model for human cancer vaccine development. IDO and RhoC, both important in human cancer development and progression, were used as vaccine targets and 12 pigs were immunized with overlapping 20mer peptides spanning the entire porcine IDO and RhoC sequences formulated in CTL-inducing adjuvants: CAF09, CASAC, Montanide ISA 51 VG, or PBS. Taking advantage of recombinant swine MHC class I molecules (SLAs), the peptide-SLA complex stability was measured for 198 IDO- or RhoC-derived 9-11mer peptides predicted to bind to SLA-1(*)04:01, -1(*)07:02, -2(*)04:01, -2(*)05:02, and/or -3(*)04:01. This identified 89 stable (t½ ≥ 0.5 h) peptide-SLA complexes. By IFN-γ release in PBMC cultures we monitored the vaccine-induced peptide-specific CTL responses, and found responses to both IDO- and RhoC-derived peptides across all groups with no adjuvant being superior. These findings support the further use of pigs as a large animal model for vaccine development against human cancer.
Insights
Pigs show promise as a large animal model for human cancer vaccine development. Immunization with IDO and RhoC peptides induced cytotoxic T cell (CTL) responses, supporting further research in this model.
Area of Science:
- Immunology
- Oncology
- Veterinary Medicine
Background:
- Immunotherapy improves survival in metastatic cancer patients, with cancer antigens as key vaccine targets.
- Therapeutic cancer vaccine development has faced challenges, with many mouse-model-based candidates failing in human trials.
- Pigs offer a translatable large animal model for human cancer vaccine research due to similarities in antigen dose, vaccine volume, and immunome.
Purpose of the Study:
- To evaluate pigs as a supplementary large animal model for human cancer vaccine development.
- To assess the immunogenicity of IDO and RhoC cancer antigens in pigs using various adjuvants.
- To identify stable peptide-MHC complexes for monitoring vaccine-induced T cell responses.
Main Methods:
- 12 pigs were immunized with IDO and RhoC peptides formulated with adjuvants (CAF09, CASAC, Montanide ISA 51 VG, or PBS).
- Recombinant swine leukocyte antigen (SLA) class I molecules were used to measure the stability of 198 peptide-SLA complexes.
- Vaccine-induced peptide-specific cytotoxic T lymphocyte (CTL) responses were monitored via interferon-gamma (IFN-γ) release from peripheral blood mononuclear cell (PBMC) cultures.
Main Results:
- 89 stable peptide-SLA complexes (t½ ≥ 0.5 h) were identified, binding to specific SLA alleles.
- Peptide-specific CTL responses against both IDO- and RhoC-derived peptides were observed across all adjuvant groups.
- No single adjuvant demonstrated superiority in inducing T cell responses.
Conclusions:
- Pigs can serve as a valuable large animal model for human cancer vaccine development.
- The study successfully demonstrated the induction of anti-cancer peptide T cell responses in pigs.
- Further research utilizing the pig model is warranted for advancing therapeutic cancer vaccines.
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