Immunogenicity of the ALLAVGATK (gp10017-25) peptide in HLA-A3.1 melanoma patients

Chiara Castelli, Arabella Mazzocchi, Francesca Rini, Paolo Tarsini, Licia Rivoltini, Michele Maio, Gianfrancesco Gallino, Filiberto Belli, Giorgio Parmiani

Research output: Contribution to journalArticle

Abstract

A T cell line recognizing autologous and allogeneic HLA-A3.1 melanomas was obtained from a disease-free melanoma patient (patient 15,392). By transfection of a tumor cDNA library and in vitro sensitization experiments, the ALLAVGATK gp100/Mel17-derived peptide was found to be the epitope recognized by this melanoma-specific T cell line. The role of the ALLAVGATK peptide in the systemic immune response to melanoma of this patient was evaluated. When pulsed on the autologous peripheral blood mononuclear cells, the ALLAVGATK peptide generated tumor-specific HLA-A3-restricted T lymphocytes and a single restimulation in vitro was sufficient to raise gp100-specific T lymphocytes, indicating a high frequency of epitope-specific T cells. gp100-specific T cells were also induced from T lymphocytes purified from tumor-invaded lymph nodes (tumor-associated lymphocytes, TAL). TAL-derived effectors displayed lower peptide affinity and lower tumor recognition than effectors elicited from peripheral blood lymphocytes (PBL). To further evaluate its immunogenicity, ALLAVGATK was used to stimulate PBL derived from six additional HLA-A3.1 melanoma patients and seven healthy donors. After 7 weeks of peptide stimulation in vitro the generation of anti-gp100 and tumor-specific T cell lines was achieved in one out of the six patients analyzed. Taken together these data indicate that an in vivo priming leading to a systemic immunity against gp100 in HLA-A3 melanoma patients may occasionally occur and that the immunogenicity of ALLAVGATK peptide in melanoma patients is comparable to that of other HLA-A2-restricted epitopes derived from gp100/Mel17 protein.

Original languageEnglish
Pages (from-to)1143-1154
Number of pages12
JournalEuropean Journal of Immunology
Volume28
Issue number4
DOIs
Publication statusPublished - Apr 1998

Keywords

  • Human
  • Immunotherapy
  • Tumor antigen
  • Tumor-infiltrating lymphocyte

ASJC Scopus subject areas

  • Immunology

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