Cancer immunotherapy with Mucin-1 and cytokines

Cancer immunotherapy involves the manipulation of the immune response to combat tumour cells. The studies contained within investigated the role of cytokines in the anti-tumour immune response to the cancer antigen, MUCl, which is over produced in an altered form in cancers of the breast, pancreas, and ovary making an ideal target for immunotherapy. MUCl coupled to oxidised mannan (MFP), forms a powerful immunotherapeutic reagent capable of inducing tumour regression and cell mediated immune responses that protect against tumour challenge in many in vivo tumour models. This thesis characterised the Tl cytokine profile\ud induced from CD8+ and CD4+ T cells following immunisation with MFP and suggested a role for IL-12 in the MUCl anti-tumour immune response. The addition of various combinations\ud of Tl and T2 cytokines to MFP injections considerably increased the MUCl CTLp response, and demonstrated a role for IL-5 in the induction of cytotoxic T cells. A MUCl mammary carcinoma tumour was characterised to provide a more realistic model for MUCl immunotherapy studies. However, of particular significance was the discovery that additional IL-12 included in MFP immunisations,considerably decreases tumour growth in MUCl transgenic mice and significantly increases the MUCl specific CTLp response. The use of IL-12 and MFP in cancer immunotherapy has now progressed into Phase I human clinical trials in cancer patients