CIRCULATING MELAN-A MART-1 SPECIFIC CYTOLYTIC T-LYMPHOCYTE PRECURSORSIN HLA-A2(+) MELANOMA PATIENTS HAVE A MEMORY PHENOTYPE/

Melan-A/MART-1 is a melanoma differentiation antigen that is recognize d by a high proportion of cytolytic T lymphocyte (CTL) clones derived from human leukocyte antigen (HLA)-A2(+) melanoma patients. Whereas pe ptide Melan-A/MART-1(27-35) was originally defined as the immunodomina nt CTL epitope, we have previously reported that peptide Melan-A/MART- 1(26-35) was recognized more efficiently by the majority of tumor-reac tive CTL clones. As demonstrated here, CTL populations generated from blood lymphocytes of either melanoma patients or healthy individuals a fter in vitro stimulation with peptide Melan-A/MART-1(26-35) killed sp ecifically HLA-A2(+) Melan-A(+) allogeneic melanoma cells, thus sugges ting their potential use in adoptive immunotherapy. We characterized t he surface phenotype of the circulating CTL precursors (CTLp), which r espond to in vitro stimulation with peptide Melan-A/MART-1(26-35). In melanoma patients, these CTLp predominantly expressed the CD45RO memor y marker. In contrast, they were mainly, although not exclusively, fou nd in the CD45RA subpopulation of CD8(+) T cells in healthy individual s. The demonstration that Melan-A/MART-1-specific CTLp in peripheral b lood lymphocytes fi om HLA-A2(+) patients with metastatic melanoma exp ress a memory phenotype provides direct evidence that in vivo priming of this antigen may occur during tumor progression. (C) 1998 Wiley-Lis s, Inc.