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Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1.
J Immunol. 1995 Mar 01; 154(5):2257-65.JI

Abstract

MART-1 is an Ag expressed on melanomas and melanocytes, and is recognized by the majority of HLA-A2-restricted tumor-specific tumor-infiltrating lymphocytes (TIL) from melanoma patients. In the present study we have analyzed 10 potential 9-mer epitopes containing the HLA-A2.1 binding motifs for their ability to induce melanoma-specific T cell lines. Antimelanoma CTL could be generated only with MART-1(27-35) peptide, which has been previously shown to be recognized by a majority of HLA-A2-restricted TIL. Anti-MART-1(35-43)-specific CTL could also be induced, but these T cells did not recognize melanoma cells. MART-1(27-35)-specific CTL could be effectively generated from a total of 11 of 12 PBL and from 3 of 3 TIL derived from HLA-A2+ melanoma patients, as well as from 2 of 4 PBL from HLA-A2+ healthy donors by in vitro stimulation with autologous PBMC pulsed with the synthetic MART-1(27-35) peptide. These CTL lines specifically lysed and release cytokines (TNF-alpha, IFN-gamma, and GM-CSF) in response to T2 cells pulsed with MART-1(27-35), as well as to HLA-A2+ MART-1+ melanoma cells. CTL generated with MART-1(27-35) also lysed uncultured HLA-A2+ melanoma cells derived from tumor biopsies, indicating that this MART-1 epitope is likely to be expressed in association with HLA-A2 on the surface of tumor cells in vivo. CTL lines generated with MART-1(27-35) mediated 25- to 100-fold higher lytic activity than MART-1-reactive CTL grown from TIL in the presence of high dose IL-2. These results demonstrate that MART-1(27-35) peptide may represent an ideal candidate for Ag-specific immunotherapy in melanoma patients.

Authors+Show Affiliations

Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7868898

Citation

Rivoltini, L, et al. "Induction of Tumor-reactive CTL From Peripheral Blood and Tumor-infiltrating Lymphocytes of Melanoma Patients By in Vitro Stimulation With an Immunodominant Peptide of the Human Melanoma Antigen MART-1." Journal of Immunology (Baltimore, Md. : 1950), vol. 154, no. 5, 1995, pp. 2257-65.
Rivoltini L, Kawakami Y, Sakaguchi K, et al. Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1. J Immunol. 1995;154(5):2257-65.
Rivoltini, L., Kawakami, Y., Sakaguchi, K., Southwood, S., Sette, A., Robbins, P. F., Marincola, F. M., Salgaller, M. L., Yannelli, J. R., & Appella, E. (1995). Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1. Journal of Immunology (Baltimore, Md. : 1950), 154(5), 2257-65.
Rivoltini L, et al. Induction of Tumor-reactive CTL From Peripheral Blood and Tumor-infiltrating Lymphocytes of Melanoma Patients By in Vitro Stimulation With an Immunodominant Peptide of the Human Melanoma Antigen MART-1. J Immunol. 1995 Mar 1;154(5):2257-65. PubMed PMID: 7868898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1. A1 - Rivoltini,L, AU - Kawakami,Y, AU - Sakaguchi,K, AU - Southwood,S, AU - Sette,A, AU - Robbins,P F, AU - Marincola,F M, AU - Salgaller,M L, AU - Yannelli,J R, AU - Appella,E, PY - 1995/3/1/pubmed PY - 1995/3/1/medline PY - 1995/3/1/entrez SP - 2257 EP - 65 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 154 IS - 5 N2 - MART-1 is an Ag expressed on melanomas and melanocytes, and is recognized by the majority of HLA-A2-restricted tumor-specific tumor-infiltrating lymphocytes (TIL) from melanoma patients. In the present study we have analyzed 10 potential 9-mer epitopes containing the HLA-A2.1 binding motifs for their ability to induce melanoma-specific T cell lines. Antimelanoma CTL could be generated only with MART-1(27-35) peptide, which has been previously shown to be recognized by a majority of HLA-A2-restricted TIL. Anti-MART-1(35-43)-specific CTL could also be induced, but these T cells did not recognize melanoma cells. MART-1(27-35)-specific CTL could be effectively generated from a total of 11 of 12 PBL and from 3 of 3 TIL derived from HLA-A2+ melanoma patients, as well as from 2 of 4 PBL from HLA-A2+ healthy donors by in vitro stimulation with autologous PBMC pulsed with the synthetic MART-1(27-35) peptide. These CTL lines specifically lysed and release cytokines (TNF-alpha, IFN-gamma, and GM-CSF) in response to T2 cells pulsed with MART-1(27-35), as well as to HLA-A2+ MART-1+ melanoma cells. CTL generated with MART-1(27-35) also lysed uncultured HLA-A2+ melanoma cells derived from tumor biopsies, indicating that this MART-1 epitope is likely to be expressed in association with HLA-A2 on the surface of tumor cells in vivo. CTL lines generated with MART-1(27-35) mediated 25- to 100-fold higher lytic activity than MART-1-reactive CTL grown from TIL in the presence of high dose IL-2. These results demonstrate that MART-1(27-35) peptide may represent an ideal candidate for Ag-specific immunotherapy in melanoma patients. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7868898/Induction_of_tumor_reactive_CTL_from_peripheral_blood_and_tumor_infiltrating_lymphocytes_of_melanoma_patients_by_in_vitro_stimulation_with_an_immunodominant_peptide_of_the_human_melanoma_antigen_MART_1_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=7868898 DB - PRIME DP - Unbound Medicine ER -