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Preclinical HER-2 Vaccines: From Rodent to Human HER-2
Pier-Luigi Lollini1, Carla De Giovanni, Patrizia Nanni
1Laboratory of Immunology and Biology of Metastases, Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum University of Bologna , Bologna , Italy.
Abstract:
Effective prevention of human cancer with vaccines against viruses, such as HBV and HPV, raises the question whether also non-virus related tumors could be prevented with immunological means. Studies in HER-2-transgenic mice showed that powerful anti-HER-2 vaccines, could almost completely prevent the onset of mammary carcinoma. Protective immune responses were orchestrated by T cells and their cytokines, and effected by antibodies against HER-2 gene product p185. Analogous findings were reported in a variety of other cancer immunoprevention systems, thus leading to the definition of oncoantigens, optimal target antigens that are causally involved in carcinogenesis and cancer progression. Prophylactic HER-2 vaccines were also effective in preventing metastasis outgrowth, indicating that concepts and approaches developed for cancer immunoprevention could prove fruitful in cancer immunotherapy as well. The availability of cancer-prone mice carrying a human HER-2 transgene is now fostering the design of novel vaccines against human p185. A further bridge toward human cancer was recently provided by novel immunodeficient models, like Rag2(-/-);Il2rg(-/-) mice, which are permissive for metastatic spread of human HER-2+ cancer cells and can be engrafted with a functional human immune system, allowing for the first time the study of vaccines against oncoantigens to elicit human immune responses against human cancer cells in vivo.
Insights
Cancer vaccines targeting oncoantigens, like HER-2, show promise in preventing tumors. Research in mice demonstrates that anti-HER-2 vaccines can prevent mammary carcinoma and metastasis, paving the way for human cancer prevention strategies.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Viral vaccines (HBV, HPV) prevent cancer, prompting research into non-viral tumor prevention.
- HER-2 transgenic mouse models develop mammary carcinoma, serving as a model for cancer immunoprevention studies.
Purpose of the Study:
- To investigate the potential of immunological approaches for preventing non-virus-related cancers.
- To evaluate the efficacy of anti-HER-2 vaccines in preventing mammary carcinoma and metastasis in preclinical models.
Main Methods:
- Utilized HER-2 transgenic mice to test the efficacy of anti-HER-2 vaccines.
- Analyzed the role of T cells, cytokines, and antibodies in vaccine-induced protection.
- Employed novel immunodeficient mouse models (Rag2(-/-);Il2rg(-/-)) engrafted with human immune systems to study human immune responses against human cancer cells.
Main Results:
- Powerful anti-HER-2 vaccines almost completely prevented mammary carcinoma onset in mice.
- Vaccines were effective in preventing metastasis outgrowth.
- Demonstrated that oncoantigens are suitable targets for cancer immunoprevention.
Conclusions:
- Cancer immunoprevention strategies targeting oncoantigens are feasible and effective.
- The findings support the development of vaccines against human HER-2 for cancer prevention and immunotherapy.
- Novel mouse models enable the study of human immune responses to oncoantigen vaccines in vivo.
