TY - JOUR T1 - Multi-target chimaeric VLP as a therapeutic vaccine in a model of colorectal cancer JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-017-0270-1 VL - 5 IS - 1 SP - 69 AU - Braeden Donaldson AU - Farah Al-Barwani AU - Simon J. Pelham AU - Katie Young AU - Vernon K. Ward AU - Sarah L. Young Y1 - 2017/12/01 UR - http://jitc.bmj.com/content/5/1/69.abstract N2 - Background Colorectal cancer is responsible for almost 700,000 deaths annually worldwide. Therapeutic vaccination is a promising alternative to conventional treatment for colorectal cancer, using vaccines to induce targeted immune responses against tumour-associated antigens. In this study, we have developed chimaeric virus-like particles (VLP), a form of non-infectious non-replicative subunit vaccine consisting of rabbit haemorrhagic disease virus (RHDV) VP60 capsid proteins containing recombinantly inserted epitopes from murine topoisomerase IIα and survivin. These vaccines were developed in mono- (T.VP60, S.VP60) and multi-target (TS.VP60) forms, aiming to elucidate the potential benefits from multi-target vaccination.Methods Chimaeric RHDV VLP were developed by recombinantly inserting immune epitopes at the N-terminus of VP60. Vaccines were tested against a murine model of colorectal cancer by establishing MC38-OVA tumours subcutaneously. Unmethylated CpG DNA oligonucleotides (CpGs) were used as a vaccine adjuvant. Statistical tests employed included the Mantel-Cox log-rank test, ANOVA and unpaired t-tests depending on the data analysed, with a post hoc Bonferroni adjustment for multiple measures.Results Chimaeric RHDV VLP were found to form a composite particle in the presence of CpGs. Overall survival was significantly improved amongst mice bearing MC38-OVA tumours following vaccination with T.VP60 (60%, 9/15), S.VP60 (60%, 9/15) or TS.VP60 (73%, 11/15). TS.VP60 significantly prolonged the vaccine-induced remission period in comparison to each mono-therapy.Conclusions Chimaeric VLP containing multiple epitopes were found to confer an advantage for therapeutic vaccination in a model of colorectal cancer based on the prolongation of remission prior to tumour escape.Abbreviations:BMDCsBone marrow-derived dendritic cellsCEACarcinoembryonic antigenCpGsUnmethylated CpG DNA OligonucleotidesCRCColorectal cancerCTLA-4Cytotoxic T Lymphocyte Associated protein 4EGFREpidermal growth factor receptorPD1Programmed Death 1RHDVRabbit haemorrhagic disease virusTAAsTumour-associated antigensTopIIαTopoisomerase IIαVEGFVascular endothelial growth factorVLPVirus-like particle ER -