Virus-like particles and 伪-galactosylceramide form a self-adjuvanting composite particle that elicits anti-tumor responses

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• 作者：Sara J. McKee^a ; ^b ; ^f ; ^{smckee@malaghan.org.nz} ; Vivienne L. Young^b ; Fiona Clow^c ; ^{f.clow@auckland.ac.nz} ; Colin M. Hayman^d ; ^{c.hayman@irl.cri.nz} ; Margaret A. Baird^b ; ^{margaret.baird@otago.ac.nz} ; Ian F. Hermans^a ; ^e ; ^{ihermans@malaghan.org.nz} ; Sarah L. Young^f ; ^{sarah.young@otago.ac.nz} ; Vernon K. Ward^b ; ^{vernon.ward@otago.ac.nz}
• 关键词：Virus-like particle ; RHDV ; Calicivirus ; 伪-Galactosylceramide ; Anti-tumor
• 刊名：Journal of Controlled Release
• 出版年：2012
• 期刊代码：25_01683659
• 类别：pha
• 出版时间：10 May, 2012
• 卷：159
• 期：3
• 页码：338-345
• 文件大小：774 K

摘要

Virus-like particles (VLP) are effective vehicles for delivery of heterologous antigen to antigen-presenting cells. However VLP alone are insufficiently stimulatory to generate the signals required to facilitate effective priming of na茂ve T cells. We show that the VLP derived from rabbit hemorrhagic disease virus can bind the galactose-containing adjuvant 伪-galactosylceramide to form a composite particle for co-delivery of antigen and adjuvant to the same antigen-presenting cell. Vaccination with VLP and 伪-galactosylceramide activated splenic iNKT cells to produce IFN-纬 and IL-4, led to the generation of antigen-specific T cells that protected prophylactically against subcutaneous tumor challenge, and was more effective at generating anti-tumor immune responses than either component individually. These data demonstrate a novel method for immunopotentiating VLP to increase their efficacy in the generation of anti-tumor responses via the innate ligand recognition properties of calicivirus-derived nanoparticles.