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All in one: VLP‐MUC1 vaccine for prevention and treatment of epithelial tumors

A promising target for immunotherapy, both for prophylactic and therapeutic vaccines, is the tumor antigen MUC1. Normally, the MUC1 glycoprotein is expressed at low levels on epithelial cells. However, MUC1 is hypoglycosylated and overexpressed on most adenocarcinomas of breast, pancreas, colon, ovary and lung. The goal of this project is to test a safe, practical and potentially very effective MUC1 vaccine using bovine papillomavirus like particles (BPV VLP) as a MUC1 delivery vehicle. BPV contains 2 capsid proteins, L1 and L2. L1 protein is made up of 12 β strands, 6 loops and 5 α helices and can self‐assemble into VLP. To enable conjugation of MUC1 and VLP, substitutions were made in the loop regions of the L1 molecule. Successful VLP formation following loop substitutions was achievable only in the HI loop where eight amino acids were replaced with negatively charged glutamic acid residues followed by a cysteine. Further, the MUC1 peptide was preceded by seven positively charged arginine and one cysteine residue. These substitutions allow the formation of a polyionic and a covalent bond that strengthens the conjugation between VLP and MUC1. Our preliminary results show that VLP‐MUC1 can cause the maturation of DC and that these DC can process and present the MUC1 peptide to a MUC1 specific T cell hybridoma. The potential of this vaccine to elicit an immune response, as well as tumor rejection is currently being evaluated.