Human ErbB-2 (Her-2) transgenic mice: a model system for testing Her-2 based vaccines

Area of Science:

• Immunology
• Oncology
• Genetics

Background:

• The human epidermal growth factor receptor 2 (Her-2) is a key target in cancer therapy.
• Developing effective Her-2 vaccines requires animal models that mimic human immune responses and tolerance.
• Transgenic models expressing human Her-2 are crucial for pre-clinical vaccine evaluation.

Purpose of the Study:

• To generate and characterize Her-2 transgenic (Tg) mice for Her-2 vaccine testing.
• To assess the immune tolerance to human Her-2 in these transgenic mice.
• To evaluate the efficacy of DNA vaccination in overcoming Her-2 tolerance.

Main Methods:

• Generation of Her-2 Tg mice using a whey acidic protein promoter driving human c-ErbB-2 expression.
• Verification of ErbB-2 expression in mammary epithelia and cerebellar glia.
• Assessment of Her-2 tolerance via syngenic tumor challenge.
• Immunization with plasmid DNA encoding secErbB-2 and GM-CSF, followed by tumor challenge.

Main Results:

• Her-2 Tg mice expressed human ErbB-2 in specific tissues without neoplastic transformation.
• These mice demonstrated tolerance to Her-2, allowing tumor growth without an antibody response.
• DNA vaccination led to partial rejection of Her-2 expressing tumors in approximately 33% of Her-2 Tg mice.

Conclusions:

• Her-2 Tg mice exhibit Her-2 expression and tolerance, mirroring human conditions.
• These mice serve as a valuable model for testing Her-2 based vaccines.
• The partial overcoming of tolerance by DNA vaccination suggests potential for therapeutic strategies.