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Published on: February 24, 2023
Vaccine-induced ErbB (EGFR/HER2)-specific immunity in spontaneous canine cancer
Hester A Doyle1, Renelle J Gee1, Tyler D Masters1
1Section of Rheumatology, Yale School of Medicine, P.O. Box 208031, New Haven, CT 06520-8031, USA.
Abstract:
Epidermal Growth Factor Receptor (EGFR) is overexpressed on a number of human cancers, and often is indicative of a poor outcome. Treatment of EGFR/HER2 overexpressing cancers includes monoclonal antibody therapy (cetuximab/trastuzumab) either alone or in conjunction with other standard cancer therapies. While monoclonal antibody therapy has been proven to be efficacious in the treatment of EGFR/HER2 overexpressing tumors, drawbacks include the lack of long-lasting immunity and acquired resistance to monoclonal therapy. An alternative approach is to induce a polyclonal anti-EGFR/HER2 tumor antigen response by vaccine therapy. In this phase I/II open-label study, we examined anti-tumor immunity in companion dogs with spontaneous EGFR expressing tumors. Canine cancers represent an outbred population in which the initiation, progression of disease, mutations and growth factors closely resemble that of human cancers. Dogs with EGFR expressing tumors were immunized with a short peptide of the EGFR extracellular domain with sequence homology to HER2. Serial serum analyses demonstrated high titers of EGFR/HER2 binding antibodies with biological activity similar to that of cetuximab and trastuzumab. Canine antibodies bound both canine and human EGFR on tumor cell lines and tumor tissue. CD8 T cells and IgG deposition were evident in tumors from immunized dogs. The antibodies inhibited EGFR intracellular signaling and inhibited tumor growth in vitro. Additionally, we illustrate objective responses in reducing tumors at metastatic sites in host animals. The data support the approach of amplifying anti-tumor immunity that may be relevant in combination with other immune modifying therapies such as checkpoint inhibitors.
Insights
This study shows that a vaccine targeting Epidermal Growth Factor Receptor (EGFR) can generate an immune response in dogs with cancer. This approach may offer a new way to treat EGFR-expressing tumors, potentially improving long-term immunity.
Area of Science:
- Oncology
- Immunology
- Veterinary Medicine
Background:
- Epidermal Growth Factor Receptor (EGFR) overexpression is common in many human cancers, correlating with poor prognosis.
- Current treatments like monoclonal antibodies (cetuximab/trastuzumab) face challenges such as limited long-lasting immunity and acquired resistance.
- Vaccine therapy offers an alternative by inducing a polyclonal anti-EGFR/HER2 tumor antigen response.
Purpose of the Study:
- To investigate the anti-tumor immunity induced by a novel vaccine in companion dogs with spontaneous EGFR-expressing tumors.
- To evaluate the biological activity and efficacy of induced canine antibodies against EGFR/HER2.
- To assess the potential of this vaccine approach in a naturally occurring cancer model that mirrors human disease.
Main Methods:
- A phase I/II open-label study involving companion dogs with EGFR-expressing tumors.
- Immunization with a short peptide from the EGFR extracellular domain with sequence homology to HER2.
- Serial serum analysis for antibody titers and biological activity, tumor tissue analysis for immune cell infiltration and antibody deposition, and in vitro assays for EGFR signaling inhibition and tumor growth.
- Evaluation of tumor response in metastatic sites.
Main Results:
- High titers of EGFR/HER2 binding antibodies were observed, exhibiting biological activity similar to cetuximab and trastuzumab.
- Canine antibodies demonstrated binding to both canine and human EGFR on tumor cell lines and tissues.
- Evidence of CD8 T cell infiltration and IgG deposition within tumors of immunized dogs.
- Inhibition of EGFR intracellular signaling and tumor growth in vitro, with objective responses observed in reducing metastatic tumors in vivo.
Conclusions:
- Vaccine-induced antibodies show significant anti-tumor activity against EGFR-expressing tumors in dogs.
- Canine EGFR-expressing tumors serve as a relevant model for studying anti-EGFR/HER2 vaccine efficacy.
- This approach holds promise for enhancing anti-tumor immunity, potentially in combination with other immunotherapies like checkpoint inhibitors.
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