Development of a CTL vaccine for Her-2/neu using peptide-microspheres and adjuvants
| Autor: | Martin A. Cheever, Sally Mossman, Kenneth H. Grabstein, H. Fang, Lawrence Evans, Mark E. Johnson, Syamal Raychaudhuri, Thomas R. Tice, Jay K. Staas |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
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 |
| Zdroj: | Vaccine. 23:3545-3554 |
| ISSN: | 0264-410X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect