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CTL activation using the natural low-affinity epitope 222-229 from tyrosinase-related protein 1 leads to tumor rejection.
- Source :
-
Cancer research [Cancer Res] 2009 Apr 01; Vol. 69 (7), pp. 3114-20. Date of Electronic Publication: 2009 Mar 10. - Publication Year :
- 2009
-
Abstract
- Vaccine strategies for cancer immunotherapy have focused on peptide ligands with high affinity for MHC class I. Largely, these vaccines have not been therapeutic. We have examined the peptide specificity of a strongly protective T-cell response that eradicates established B16 melanoma and find that the recognized epitope is generated by a low-affinity MHC class I ligand from tyrosinase-related protein 1 (TRP1). Cytotoxic T-cell responses are induced against TRP1(222-229) by several vaccination schemes using a Toll-like receptor agonist, T regulatory cell depletion, or the immune modulator B7-DCXAb to drive immunity. TRP1(222) CTL are generated from multiple antigen sources, including antigens expressed by tumors growing in situ, tumor cell lysates, and peptide vaccines. The key finding in this study is that protection from freshly implanted or established B16 tumors is primarily mediated by TRP1(222)-specific CTL and not by CTL specific for more traditional melanoma antigens such as TRP2 or gp100. This finding challenges the assumption that the optimal peptide antigens for cancer vaccines are high-affinity MHC ligands. We propose that when administered appropriately, native low-affinity MHC ligands are optimal inducers of immunotherapeutic CTL.
- Subjects :
- Animals
Antibodies immunology
Antibodies pharmacology
Antigens, Neoplasm immunology
B7-1 Antigen immunology
Cancer Vaccines immunology
Cell Growth Processes immunology
Immunodominant Epitopes immunology
Interferon-gamma immunology
Lymphocyte Activation
Melanoma, Experimental pathology
Melanoma, Experimental therapy
Mice
Mice, Inbred C57BL
Programmed Cell Death 1 Ligand 2 Protein
Epitopes, T-Lymphocyte immunology
Melanoma, Experimental immunology
Membrane Glycoproteins immunology
Oxidoreductases immunology
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 69
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 19276379
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-08-2448