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Development of a CTL vaccine for Her-2/neu using peptide-microspheres and adjuvants
- Source :
- Vaccine. 23:3545-3554
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- 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 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.
- Subjects :
- Cytotoxicity, Immunologic
Receptor, ErbB-2
medicine.medical_treatment
Mice, Transgenic
Peptide
Cancer Vaccines
Mice
Adjuvants, Immunologic
Animals
Humans
Medicine
Cytotoxic T cell
Polyglactin 910
Cells, Cultured
chemistry.chemical_classification
General Veterinary
General Immunology and Microbiology
business.industry
Public Health, Environmental and Occupational Health
Microspheres
Peptide Fragments
Vaccination
CTL
Infectious Diseases
Immunization
chemistry
Immunology
Molecular Medicine
Female
Cancer vaccine
business
Adjuvant
Spleen
CD8
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 0264410X
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Vaccine
- Accession number :
- edsair.doi.dedup.....87e3f02ebc49d1c3088e46c41d82b8ac