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.
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/N(neu) 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.
University of Glasgow, Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, UK. Electronic address: Arunima.Mukhopadhyay@glasgow.ac.uk.
Arunima
A
Mukhopadhyay
ExpreS2ion Biotechnologies, Agern Allé 1, 2970 Horsholm, Denmark.
Charlotte
C
Dyring
University of Glasgow, Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
David I
DI
Stott
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D007135:Immunoglobulin Variable Region; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins
Antibody; Breast cancer; ErbB-2; H; Ig; Mouse model; Repertoire; Tolerance; V; V-genes; cDNA; complementary DNA; heavy; immunoglobulin; variable