CTL activation using the natural low-affinity epitope 222-229 from tyrosinase-related protein 1 leads to tumor rejection

Kevin D. Pavelko, Michael J. Hansen, Larry R Pease

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 (TRFl). Cytotoxic T-cell responses are induced against TRPI222-229 by several vaccination schemes using a Toll-like receptor agonist, T regulatory cell depletion, or the immune modulator B7- DCXAb to drive immunity. TRPI222 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 TRPl222-specific CTL and not by CTL specific for more traditional melanoma antigens such as TRP2 or gplOO. 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.

Original languageEnglish (US)
Pages (from-to)3114-3120
Number of pages7
JournalCancer Research
Volume69
Issue number7
DOIs
StatePublished - Apr 1 2009

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Epitopes
Ligands
Cancer Vaccines
Peptides
Neoplasms
Melanoma-Specific Antigens
T-Lymphocytes
Antigens
Experimental Melanomas
Subunit Vaccines
Toll-Like Receptors
Neoplasm Antigens
Regulatory T-Lymphocytes
Immunotherapy
Immunity
Vaccination
Vaccines
tyrosinase-related protein-1
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

CTL activation using the natural low-affinity epitope 222-229 from tyrosinase-related protein 1 leads to tumor rejection. / Pavelko, Kevin D.; Hansen, Michael J.; Pease, Larry R.

In: Cancer Research, Vol. 69, No. 7, 01.04.2009, p. 3114-3120.

Research output: Contribution to journalArticle

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