PARAMETERS FOR USING MANNAN-MUC1 FUSION PROTEIN TO INDUCE CELLULAR-IMMUNITY

We have previously reported preclinical studies in mice of the human m ucin 1 (MUC1) antigen covalently linked to the yeast cell-wall mannan polysaccharide (MFP), and shown strong cellular responses of the T1 ty pe using mice. We now describe the optimum parameters for admin istrat ion of MFP to obtain cellular immunity Cas measured by the cytotoxic T cell precursor (CTLp) frequency]. In dose/response studies, in which 1 mu g-150 mu g was given by the i.p. route, it was clear that doses o f 1-7 mu g led to cellular and not humoral immunity; at doses above 7 mu g humoral immunity prevailed with little cellular immunity increasi ng doses giving greater amounts of antibody. The most favoured routes of administration were intraperitoneal or intradermal immunisation, wh ich were substantially better than i.m., i.v.; s.c. administration was the worst. Three immunisations were necessary for a maximum cellular response, further immunisation decreasing the CTLp frequency. Six diff erent adjuvants were used with MFP [complete and incomplete Freund's a djuvant (CFA, IFA) Alum, Adjuprime, muramyl dipeptide (MDP) and glutam inyl-muramyl dipeptide (GMDP)I; Alum, GMDP, MDP and LFA moderately inc reased the CTLp frequency, IFA being the best. Even though preclinical studies of the immunogen in mice may not necessarily mirror the behav iour of the immunogen in humans, these studies demonstrate the factors to be taken into account for phase I/II clinical trials.