MELANOMA TUMOR-INFILTRATING LYMPHOCYTES DERIVED FROM 4 DISTINCT ANATOMIC SITES OBTAINED FROM A SINGLE PATIENT - COMPARISON OF FUNCTIONAL REACTIVITY AND MELANOMA ANTIGEN RECOGNITION

Tumor-infiltrating lymphocytes (TILs) were grown from four distinct an atomic sites from a patient with metastatic melanoma. The metastatic s ites included a tumor-involved lymph node, a subcutaneous lesion obtai ned from the chest wall, a portion of bowel, and adrenal gland. TILs g rown from each anatomic site over the course of 20 days in the presenc e of 6,000 IU/ml recombinant interleukin-2 exhibited comparable growth rates. Between days 30 and 45, the TILs were a mixture of CD3(+) CD4( +) and CD3(+) CD8(+) lymphocytes expressing the alpha beta form of the T-cell receptor. TILs derived from each anatomic site specifically ly sed autologous tumor obtained from all four anatomic sites. In fine sp ecificity analysis, the TILs exhibited human leukocyte antigen (HLA-A2 )-restricted lysis of fresh tumor targets and cultured melanoma cell l ines. Each TIL recognized a product of the MART-1 gene, and specifical ly, the monomer peptide MART-1(27-35). Thus lymphocytes reactive with the MART-1 melanoma antigen appeared to be widely distributed in diver se metastases in this patient. This information, along with previous d ata on the reactivity of multiple patients to this antigen, attests to its dominance in the immune reactivity of humans to melanoma.