Establishing the pig as a large animal model for vaccine development against human cancer

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.

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

“…We tested RBD-SpyVLP for its immunogenicity in pigs as a large, genetically outbred animal model. Pigs have previously been reported to be a reliable model to study vaccines for use in humans because of their highly similar physiologies and immune systems 32,33 . The pig model has been used recently to test an adenovirus vector vaccine candidate against SARS-CoV-2 (ChAdOx1 nCoV19) 34 .…”

Induction and characterization of pancreatic cancer in a transgenic pig model

“…Furthermore, new cancer therapies developed in rodents have a high failure rate when translated to humans [16]. Presumably this is due to differences in physiology [17,18], drug dosing [19,20], and immune response [21][22][23][24] between rodents and humans.…”

Genetically Induced Tumors in the Oncopig Model Invoke an Antitumor Immune Response Dominated by Cytotoxic CD8β+ T Cells and Differentiated γδ T Cells Alongside a Regulatory Response Mediated by FOXP3+ T Cells and Immunoregulatory Molecules

“…Beyond differences in disease pathogenesis and progression between rodents and humans ( 3 – 5 ), the size constraints of rodents often do not support the investigation of new surgical interventions ( 4 , 6 ). In light of the numerous obstacles presented by rodent models of disease, alternative model systems have been proposed, including zebrafish ( 7 , 8 ), cats ( 9 ), dogs ( 9 – 14 ), and pigs ( 15 – 22 ). Due to homology in physiology, anatomy, size, genetics, metabolism, life span, and immunome between humans and pigs ( 15 , 23 – 25 ), a porcine model may be extremely relevant for preclinical testing of cancer treatments.…”

“…In light of the numerous obstacles presented by rodent models of disease, alternative model systems have been proposed, including zebrafish ( 7 , 8 ), cats ( 9 ), dogs ( 9 – 14 ), and pigs ( 15 – 22 ). Due to homology in physiology, anatomy, size, genetics, metabolism, life span, and immunome between humans and pigs ( 15 , 23 – 25 ), a porcine model may be extremely relevant for preclinical testing of cancer treatments. Furthermore, in contrast to murine cells, both porcine and human somatic cells demonstrate suppressed telomerase activity in most tissues that is reactivated during cancer development ( 26 , 27 ).…”