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HLA-A3 restricted mutant ras specific cytotoxic T-lymphocytes induced by vaccination with T-helper epitopes.
J Mol Med (Berl). 2003 Jan; 81(1):43-50.JM

Abstract

Cytotoxic T-lymphocytes are one of the most important elements of the antitumor defense. Stimulation of cytotoxic T-lymphocytes outgrowth after immunization with mutant ras peptides is a desired goal since these cells may kill tumor cells in vivo. In this study we tested responding peripheral mononuclear cells from a patient with pancreatic adenocarcinoma who had received intradermal peptide vaccination with a mixture of 17-mer mutant ras peptides and granulocyte-macrophage colony-stimulating factor as an adjuvant. Responding peripheral T-cells were cloned by limiting dilution and several CD8(+) cytotoxic T-lymphocytes, specific for the K- RAS 12-Cys mutation were obtained. By using a panel of nonamer peptides containing the 12-Cys mutation and covering position 4-21 in the ras molecule, the 9-mer peptide which was actually recognized by the cytotoxic T-lymphocytes could be identified. HLA-A*0302 could be identified as the antigen-presenting molecule, and the amino acid sequence of the T-cell epitope carries the previously identified HLA-A*0302 binding motif. The nonamer peptide was contained within the vaccine peptide originally used for intradermal immunization of the patient. The cytotoxic T-lymphocytes were capable of killing target cells expressing HLA-A*0302 that coexpressed the K- RAS 12-Cys mutation after transfection. These data demonstrate that the peptide used for vaccination (17-mer) is processed and presented in vivo, and that generation of cytotoxic T-lymphocytes by vaccination with T-helper epitopes may be important for further development of specific immunotherapy of cancer patients.

Authors+Show Affiliations

Section for Immunotherapy, Department of Immunology, Norwegian Radium Hospital, University of Oslo, Montebello, 0310 Oslo, Norway. m.k.gjertsen@labmed.uio.noNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12545248

Citation

Gjertsen, Marianne Klemp, et al. "HLA-A3 Restricted Mutant Ras Specific Cytotoxic T-lymphocytes Induced By Vaccination With T-helper Epitopes." Journal of Molecular Medicine (Berlin, Germany), vol. 81, no. 1, 2003, pp. 43-50.
Gjertsen MK, Saeterdal I, Saebøe-Larssen S, et al. HLA-A3 restricted mutant ras specific cytotoxic T-lymphocytes induced by vaccination with T-helper epitopes. J Mol Med. 2003;81(1):43-50.
Gjertsen, M. K., Saeterdal, I., Saebøe-Larssen, S., & Gaudernack, G. (2003). HLA-A3 restricted mutant ras specific cytotoxic T-lymphocytes induced by vaccination with T-helper epitopes. Journal of Molecular Medicine (Berlin, Germany), 81(1), 43-50.
Gjertsen MK, et al. HLA-A3 Restricted Mutant Ras Specific Cytotoxic T-lymphocytes Induced By Vaccination With T-helper Epitopes. J Mol Med. 2003;81(1):43-50. PubMed PMID: 12545248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HLA-A3 restricted mutant ras specific cytotoxic T-lymphocytes induced by vaccination with T-helper epitopes. AU - Gjertsen,Marianne Klemp, AU - Saeterdal,Ingvil, AU - Saebøe-Larssen,Stein, AU - Gaudernack,Gustav, Y1 - 2002/11/13/ PY - 2002/06/17/received PY - 2002/09/02/accepted PY - 2003/1/25/pubmed PY - 2003/10/3/medline PY - 2003/1/25/entrez SP - 43 EP - 50 JF - Journal of molecular medicine (Berlin, Germany) JO - J. Mol. Med. VL - 81 IS - 1 N2 - Cytotoxic T-lymphocytes are one of the most important elements of the antitumor defense. Stimulation of cytotoxic T-lymphocytes outgrowth after immunization with mutant ras peptides is a desired goal since these cells may kill tumor cells in vivo. In this study we tested responding peripheral mononuclear cells from a patient with pancreatic adenocarcinoma who had received intradermal peptide vaccination with a mixture of 17-mer mutant ras peptides and granulocyte-macrophage colony-stimulating factor as an adjuvant. Responding peripheral T-cells were cloned by limiting dilution and several CD8(+) cytotoxic T-lymphocytes, specific for the K- RAS 12-Cys mutation were obtained. By using a panel of nonamer peptides containing the 12-Cys mutation and covering position 4-21 in the ras molecule, the 9-mer peptide which was actually recognized by the cytotoxic T-lymphocytes could be identified. HLA-A*0302 could be identified as the antigen-presenting molecule, and the amino acid sequence of the T-cell epitope carries the previously identified HLA-A*0302 binding motif. The nonamer peptide was contained within the vaccine peptide originally used for intradermal immunization of the patient. The cytotoxic T-lymphocytes were capable of killing target cells expressing HLA-A*0302 that coexpressed the K- RAS 12-Cys mutation after transfection. These data demonstrate that the peptide used for vaccination (17-mer) is processed and presented in vivo, and that generation of cytotoxic T-lymphocytes by vaccination with T-helper epitopes may be important for further development of specific immunotherapy of cancer patients. SN - 0946-2716 UR - https://www.unboundmedicine.com/medline/citation/12545248/HLA_A3_restricted_mutant_ras_specific_cytotoxic_T_lymphocytes_induced_by_vaccination_with_T_helper_epitopes_ L2 - https://dx.doi.org/10.1007/s00109-002-0390-y DB - PRIME DP - Unbound Medicine ER -