Abstract
Lipid-based formulations (liposomes and W/O/W double emulsions) were developed for oral delivery of a peptide vaccine to treat colorectal cancer. Immune responses generated following oral delivery of the vaccines were examined in tumour-free mice and in mice with an established orthotopic colorectal cancer. Vaccination of mice resulted in activation of lymphocyte subsets in the lymph nodes, spleen and tumour and reduced tumour growth.
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The aim of this study was to develop an oral vaccine that could be used to treat colorectal cancer. Oral vaccines are technically challenging to develop due to the harsh gastric environment but have numerous benefits including high patient acceptability and the potential to stimulate local mucosal immune responses. Therapeutic vaccines are being investigated as options to treat cancer and the generation of local mucosal immunity may be of benefit in the treatment of gastrointestinal cancers. Novel oral vaccines consisting of a long tumour peptide and the TLR2 (Toll-like receptor 2) ligand Pam2Cys, formulated in either liposomes or W/O/W double emulsions, were developed. Oral dosing with the emulsion vaccine increased the numbers of activated T cells, B cells and CD11c+F4/80+CD11b+ cells compared to mice that received control vaccines. In an orthotopic mouse model of colorectal cancer these immunological changes were associated with a seven-fold reduction in tumour size.