Evolution of animal models in cancer vaccine development

Wei, Wei Zen; Jones, Richard F.; Juhász, Csaba; Gibson, Heather M.; Veenstra, Jesse

doi:10.1016/j.vaccine.2015.07.075

Cited by 15 publications

(10 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we did not show the protective or preventive immune responses in animal model after the vaccination of the GA P × CO P . In the future, it is required to determine protective immunity of GA P × CO P against cancer induced in animal model with its vaccination [45]. In addition, in vitro migration or wounding healing assays would be essential to investigate the anti-metastasis activity of the anticancer IgGs induced in the vaccinated mice [29,46].…”

Section: Discussionmentioning

confidence: 99%

A Plant-Derived Antigen–Antibody Complex Induces Anti-Cancer Immune Responses by Forming a Large Quaternary Structure

Kim

Kang

Lee

et al. 2020

IJMS

View full text Add to dashboard Cite

The antigen–antibody complex (AAC) has novel functions for immunomodulation, encouraging the application of diverse quaternary protein structures for vaccination. In this study, GA733 antigen and anti-GA733 antibody proteins were both co-expressed to obtain the AAC protein structures in a F1 plant obtained by crossing the plants expressing each protein. In F1 plant, the antigen and antibody assembled to form a large quaternary circular ACC structure (~30 nm). The large quaternary protein structures induced immune response to produce anticancer immunoglobulins G (IgGs) that are specific to the corresponding antigens in mouse. The serum containing the anticancer IgGs inhibited the human colorectal cancer cell growth in the xenograft nude mouse. Taken together, antigens and antibodies can be assembled to form AAC protein structures in plants. Plant crossing represents an alternative strategy for the formation of AAC vaccines that efficiently increases anticancer antibody production.

show abstract

Section: Discussionmentioning

confidence: 99%

A Plant-Derived Antigen–Antibody Complex Induces Anti-Cancer Immune Responses by Forming a Large Quaternary Structure

Kim

Kang

Lee

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Immunological activity was found ex vivo in this trial, but at quite low frequencies. In contrast, high-frequency immune responses are often found in cancer immunization studies using murine models (Wei et al, 2015 ) as exemplified in the study by Zhao et al ( 2012 ), where more than 1000 pg/ml IFN-γ was secreted for most peptides tested after two immunizations and only 48 h of peptide stimulation ex vivo . For comparison, the maximum level of secreted IFN-γ observed in our trial was 280 pg/ml IFN-γ (pig 2042, day 12, peptide IDO15, Figure 3 ) following 72 h of stimulation.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

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.

show abstract

“…79,80 An ideal animal model for cancer research should preferably be fully immunocompetent to properly mimic human immune responses. 39,81 Although some mouse models are immunocompetent, they often still display a very narrow MHC class I representation due to inbreeding. Consequently, this might result in unrepresentative results when compared to outbred animals and humans.…”

Section: Genetically Engineered Mouse Modelsmentioning

confidence: 99%

Of Mice, Dogs, Pigs, and Men: Choosing the Appropriate Model for Immuno-Oncology Research

et al. 2018

View full text Add to dashboard Cite

The immune system plays dual roles in response to cancer. The host immune system protects against tumor formation via immunosurveillance; however, recognition of the tumor by immune cells also induces sculpting mechanisms leading to a Darwinian selection of tumor cell variants with reduced immunogenicity. Cancer immunoediting is the concept used to describe the complex interplay between tumor cells and the immune system. This concept, commonly referred to as the three E’s, is encompassed by 3 distinct phases of elimination, equilibrium, and escape. Despite impressive results in the clinic, cancer immunotherapy still has room for improvement as many patients remain unresponsive to therapy. Moreover, many of the preclinical results obtained in the widely used mouse models of cancer are lost in translation to human patients. To improve the success rate of immuno-oncology research and preclinical testing of immune-based anticancer therapies, using alternative animal models more closely related to humans is a promising approach. Here, we describe 2 of the major alternative model systems: canine (spontaneous) and porcine (experimental) cancer models. Although dogs display a high rate of spontaneous tumor formation, an increased number of genetically modified porcine models exist. We suggest that the optimal immuno-oncology model may depend on the stage of cancer immunoediting in question. In particular, the spontaneous canine tumor models provide a unique platform for evaluating therapies aimed at the escape phase of cancer, while genetically engineered swine allow for elucidation of tumor-immune cell interactions especially during the phases of elimination and equilibrium.

show abstract

Evolution of animal models in cancer vaccine development

Cited by 15 publications

References 91 publications

A Plant-Derived Antigen–Antibody Complex Induces Anti-Cancer Immune Responses by Forming a Large Quaternary Structure

A Plant-Derived Antigen–Antibody Complex Induces Anti-Cancer Immune Responses by Forming a Large Quaternary Structure

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

Of Mice, Dogs, Pigs, and Men: Choosing the Appropriate Model for Immuno-Oncology Research

Contact Info

Product

Resources

About