期刊
VACCINE
卷 23, 期 27, 页码 3545-3554出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2005.01.149
关键词
Her-2/neu; vaccine; microspheres; adjuvants; CTL
With the ultimate goal of developing a therapeutic cancer vaccine, we encapsulated the Her-2/neu peptide p369-377 in poly(lactide-co-glycolide) microspheres. This formulation was found to effectively elicit CD8+ cytotoxic T cell (CTL) responses in an HLA-A*0201 transgenic mouse model. In contrast, immunization with either peptide alone or peptide formulated in incomplete Freund's adjuvant (IFA) failed to elicit such CTL responses. Responses induced by the peptide-microsphere formulation were found to peak at approximately 6 weeks post-immunization, and were enhanced by delivering increased doses of peptide and with repeated administrations over time. Co-administration of the peptide-microspheres with adjuvants, including granulocyte-macrophage colony stimulating factor, MPL (R) adjuvant and select synthetic Toll-Like Receptor 4 ligands, the aminoalkyl glucosaminide-4 phosphates, significantly augmented CTL responses. These studies provide important guidance for the design of human clinical trials of microsphere vaccines in terms of optimal peptide-microsphere formulation, vaccination regimen, vaccine dose, and adjuvant selection. (c) 2005 Elsevier Ltd. All rights reserved.
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