TY - JOUR
T1 - T-cell clones from melanoma patients immunized against an anchor- modified gp100 peptide display discordant effector phenotypes
AU - Dudley, Mark E.
AU - Ngo, Lien T.
AU - Westwood, Jennifer
AU - Wunderlich, John R.
AU - Rosenberg, Steven A.
PY - 2000/3/1
Y1 - 2000/3/1
N2 - 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.
AB - 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.
KW - Cytotoxic T lymphocyte
KW - Epitopes-therapeutic use
KW - Immunotherapy-adoptive
KW - Melanoma
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M3 - Article
C2 - 11069222
AN - SCOPUS:0033941834
VL - 6
SP - 69
EP - 77
JO - Cancer journal (Sudbury, Mass.)
JF - Cancer journal (Sudbury, Mass.)
SN - 0765-7846
IS - 2
ER -