T-cell clones from melanoma patients immunized against an anchor- modified gp100 peptide display discordant effector phenotypes

Mark E. Dudley, Lien T. Ngo, Jennifer Westwood, John R. Wunderlich, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

PURPOSE: The modified peptide epitope gp100-209-217 (210M), referred to as g209-2M, of the gp100 melanocyte differentiation protein, when administered to melanoma patients by subcutaneous injection in incomplete Freund's adjuvant, is capable of generating HLA-A2-restricted CD8+ lymphocytes that specifically recognize the native gp100:209-217 (g209) peptide as well as gp100-expressing tumor cells. To evaluate the suitability of cloned lymphocytes from immunized patients for use in adoptive transfer therapy protocols, the functional and phenotypic variation of individual CD8+ T cell dunes comprising the antitumor immune response was evaluated. METHODS: T-cell clones from melanoma patients who received g209-2M immunization were isolated and expanded, and their specific antitumor functional phenotypes were characterized. RESULTS: g209-specific CD8+ lymphocytes that specially recognized gp100-expressing tumor cells were readily obtained from g209-2M-immunized patients. There was substantial variation in the absolute levels of cytokine secretion and target cell lysis by g209-specific clones from each patient. Furthermore, individual clones demonstrated discordant secretion of different proinflammatory cytokines. These clonal phenotypes were stable, even after large expansions in cell number. DISCUSSION: These results indicate that g209-2M peptide immunization of melanoma patients leads to a functionally diverse population of T cells, many of which are capable of expansion ex vivo to cell numbers appropriate for adoptive immunotherapy. However, the selection of a particular antigen- specific T-cell clone for treatment should be based on multiple functional criteria.

Original languageEnglish (US)
Pages (from-to)69-77
Number of pages9
JournalCancer Journal
Volume6
Issue number2
StatePublished - Mar 1 2000

Keywords

  • Cytotoxic T lymphocyte
  • Epitopes-therapeutic use
  • Immunotherapy-adoptive
  • Melanoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'T-cell clones from melanoma patients immunized against an anchor- modified gp100 peptide display discordant effector phenotypes'. Together they form a unique fingerprint.

  • Cite this

    Dudley, M. E., Ngo, L. T., Westwood, J., Wunderlich, J. R., & Rosenberg, S. A. (2000). T-cell clones from melanoma patients immunized against an anchor- modified gp100 peptide display discordant effector phenotypes. Cancer Journal, 6(2), 69-77.