Comparison of prophylactic and therapeutic immunisation with an ErbB-2 (HER2) fusion protein and immunoglobulin V-gene repertoire analysis in a transgenic mouse model of spontaneous breast cancer

• Effectiveness of ErbB2-P30 fusion protein vaccine in transgenic mouse model of spontaneous development of breast cancer.
• Breaking of self-tolerance with ErbB2-P30 vaccine and 100% protective antibody response after prophylactic vaccination.
• Protective effect of vaccination but not therapeutic administration against endogenous mammary carcinoma in animal model.
• Importance of spontaneous models of carcinoma compared with transplanted tumours in relation to human cancer.
• Selection for particular Vκ and VH-gene family repertoire in antibody response.

ErbB-2 is associated with several solid tumours of which breast cancer is the commonest cancer in women worldwide. Though anti-ErbB-2 antibody appears to play a significant role in prevention and therapy, naturally occurring anti-ErbB-2 antibody associated with the cleaved ectodomain of overexpressed ErbB-2 self antigen is detectable in patients. It is therefore essential to understand the course of antibody mediated protection during disease progression. 100% of FVB/Nneu mice expressing mutated, constitutively active ErbB-2 develop mammary carcinoma. It has been shown that vaccination with ErbB-2 associated with a T helper cell epitope P30 can offer protection against transplantable tumour but it is unclear whether the same vaccine protects against naturally developing tumour. We have analysed the course of the disease following prophylactic, and therapeutic vaccination in this spontaneous, eutopic mammary carcinoma model that more closely resembles the human disease. 100% protection against tumour development was observed subsequent to prophylactic immunisation but disease progression was unaffected by therapeutic vaccination. The antibody response exhibited restricted expansion of the Immunoglobulin (Ig) variable (V)-gene repertoire by ErbB-2 specific B cells compared with the non-antigen specific B cell pool and control mice. The serum antibody profile was similar in therapeutically injected mice without any effect on tumour burden.