Peptide-specific ctl in tumor-infiltrating lymphocytes from metastatic melanomas expressing mart-1/melan-a, gp100 and tyrosinase genes: A study in an unselected group of hla-a2.1-positive patients
✍ Scribed by Giulio C. Spagnoli; Christoph Schaefer; Thomas E. Willimann; Thomas Kocher; Antonio Amoroso; Antonio Juretic; Markus Zuber; Urs Luscher; Felix Harder; Michael Heberer
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- French
- Weight
- 935 KB
- Volume
- 64
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Peptide specificity of cultured tumor-infiltrating lymphocytes (TIL) was systematically investigated in a group of HLA-A2. I + metastatic melanoma patients consecutively referred to our department for surgical treatment. Seven samples from 6 patients were studied. All surgical specimens showed evidence of gp / 00, MART-I lMelan-A and Tyrosinase gene expression as detectable by reverse PCR (rPCR). Cultured TIL from 2 patients displayed cytotoxic activity against autologous or HLA-matched EBV-transformed cells previously pulsed with MART-I IMelan-A27-35 peptide. In contrast, no CTL activity against gp I 00zse2ss or tyrosina~e,_~ peptides could be observed. TIL were then repeatedly stimulated in vitro with the same peptides. After 6 restimulation courses at weekly intervals, specific recognition of gp I 0028e28e and MART-I /Melan-A27-35 peptides was detectable in 3 and 5 TIL populations, respectively. In one case Tyrosinase,-9-specific CTL could be demonstrated. Two TIL populations from metastases resected from a melanoma patient at 6 months' distance showed a different peptide specificity pattern, and no specific CTL could be generated from simultaneously sampled peripheral blood mononuclear cells (PBMC). All peptide-specific CTL populations also displayed significant cytotoxic activity against HLA-A2. I matched melanoma cell lines expressing the antigens under investigation. Our data indicate that CTL specific for MART-M~I~II-A,,-~,, gp I 0028e288 or Tyrosinasel-9 peptides could be expanded with varying frequency from TIL derived from 4 out of 6 HLA-A2.I+ patients whose tumors expressed the genes encoding these tumor-associated antigens