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

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), w...

Full description

Saved in:
Bibliographic Details
Published in:British journal of cancer 2012-01, Vol.106 (1), p.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: Article
Language:English
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2011.538