A transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human MUC1

MUC1 is a membrane bound, polymorphic epithelial mucin expressed at the lum inal surface of glandular epithelium. It is highly expressed in an undergly cosylated form on carcinomas and metastatic lesions and is, therefore, a po tential target for immunotherapy of cancer. The monoclonal antibody HMFG1 b inds the linear core protein sequence, PDTR, contained within the immunodom inant domain of the tandem repeat of MUC1. The efficacy of murine and human ized HMFG1 (Abl) used as an anti-idiotypic vaccine was examined in mice tra nsgenic for human MUC1 (MUC1.Tg) challenged with murine epithelial tumour c ells transfected with human MUC1. Humoral idiotypic cascade through Ab2 and Ab3 antibodies was observed in MUC1.Tg mice following multiple antibody in oculations in the presence of adjuvant, Impaired tumour growth at day 35 an d highest Ab3 levels were found in mice that had received mHMFG1 with RAS a djuvant, However, comparison of Ab3 levels in individual mice with tumour s ize in all treatment groups did not show a correlation between smaller tumo urs and increased levels of anti-idiotype antibody. This suggests that the anti-tumour effects of anti-idiotype vaccination are not solely related to the induction of idiotypic antibody cascades and probably involve other mec hanisms. (C) 2000 Cancer Research Campaign.