| Autor: |
Gillogly, Michael E., Kallinteris, Nikoletta L., Xu, Minzhen, Gulfo, Joseph V., Humphreys, Robert E., Murray, James L. |
| Předmět: |
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| Zdroj: |
Cancer Immunology, Immunotherapy; Jun2004, Vol. 53 Issue 6, p490-496, 7p |
| Abstrakt: |
Purpose. Cytotoxic T lymphocytes (CTL)- and T-helper cell-specific, and major histocompatibility complex (MHC) class-I and class-II peptides, respectively, of the HER-2/neu protein, induce immune responses in patients. A major challenge in developing cancer peptide vaccines is breaking tolerance to tumor-associated antigens which are functionally self-proteins. An adequate CD4+ T-helper response is required for effective and lasting responses. Methods. Stimulating anti-cancer CD4+ T cell responses by MHC class-II epitope peptides has been limited by their weak potency, at least compared with tight-binding MHC class-I epitope peptides. Previously, a potent T-cell response to a MHC class-II epitope was engineered by coupling the N-terminus of the pigeon cytochrome C [PGCC(95–104)] MHC class-II epitope to the C-terminus of an immunoregulatory segment of the Ii protein (hIi77–81, the Ii-Key peptide) through a polymethylene spacer. Results. In vitro presentation of the MHC class-II epitope to a T hybridoma was enhanced greatly (>250 times). Now, an Ii-Key/HER-2/neu (777–789) MHC class-II epitope hybrid peptide stimulated lymphocytes from both a healthy donor and a patient with metastatic breast carcinoma. The in vitro primary stimulation with the hybrid peptide strongly activated IFN-γ release, whereas the epitope-only peptide was weakly active. In fact, the hybrid stimulated IFN-γ release as well as the wild-type peptide when augmented with IL-12; however, the hybrid was comparable to free peptide in stimulating IL-4 release. This pattern is consistent with preferential activation along a non-tolerogenic Th1 pathway. Conclusion. Such Ii-Key/MHC class-II epitope hybrid peptides have both diagnostic and therapeutic applications. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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