Enhancing the immunogenicity of tumour lysate-loaded dendritic cell vaccines by conjugation to virus-like particles

• Published in: British journal of cancer Vol. 106; no. 1; pp. 92 - 98
• Main Authors: Win, S J, McMillan, D G G, Errington-Mais, F, Ward, V K, Young, S L, Baird, M A, Melcher, A A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.01.2012; Nature Publishing Group
• Subjects: Antigen presentation; Antigens; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood; Blotting, Western; Cancer Research; Cancer Vaccines - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell activation; Cytotoxicity; Dendritic cells; Dendritic Cells - immunology; Drug Resistance; Electrophoresis, Polyacrylamide Gel; Epidemiology; Epitopes; Humans; Immunogenicity; Immunotherapy; Lymphocytes; Lymphocytes T; Medical research; Medical sciences; Melanoma; Molecular Medicine; Oncology; Proteins; Subcellular Fractions; Translational Therapeutics; Tumors; Vaccines; Virion - immunology; Virus-like particles; New Zealand; United Kingdom > UK; tumour immunotherapy; lysate therapy; VLP; Pulsed dendritic cell; Lysate; Immune response; Virus like particle; Vaccine; Cancerology; Treatment; Immunogenicity; Immunotherapy; Tumor; Conjugation; Tumor cell
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2011.538

Background: Tumour cell lysates are an excellent source of many defined and undefined tumour antigens and have been used clinically in immunotherapeutic regimes but with limited success. Methods: We conjugated Mel888 melanoma lysates to rabbit haemorrhagic disease virus virus-like particles (VLP), which can act as vehicles to deliver multiple tumour epitopes to dendritic cells (DC) to effectively activate antitumour responses. Results: Virus-like particles did not stimulate the phenotypic maturation of DC although, the conjugation of lysates to VLP (VLP-lysate) did overcome lysate-induced suppression of DC activation. Lysate-conjugated VLP enhanced delivery of antigenic proteins to DC, while the co-delivery of VLP-lysates with OK432 resulted in cross-priming of naïve T cells, with expansion of a MART1 + population of CD8 + T cells and generation of a specific cytotoxic response against Mel888 tumour cell targets. The responses generated with VLP-lysate and OK432 were superior to those stimulated by unconjugated lysate with OK432. Conclusion: Collectively, these results show that the combination of VLP-lysate with OK432 delivered to DC overcomes the suppressive effects of lysates, and enables priming of naïve T cells with superior ability to specifically kill their target tumour cells.