CLONAL EXPANSION OF T-LYMPHOCYTES IN HUMAN-MELANOMA METASTASES AFTER TREATMENT WITH A HAPTEN-MODIFIED AUTOLOGOUS TUMOR VACCINE

Metastatic melanoma patients treated with an autologous DNP-modified t umor cell vaccine develop inflammatory responses in metastatic tumors characterized by infiltration of CD8+ T cells. To further define this immune response, we analyzed T cell receptor beta-chain variable (TCRB V) region repertoire in biopsy specimens and peripheral blood lymphocy tes of six patients. After administration of DNP vaccine, a restricted set of TCRBV gene families was found to be expanded compared with pre vaccine metastases. In several postvaccine lesions of one patient, obt ained over a 2-yr period, TCRBV14+ T cells were clonally expanded and identical T cell clonotypes could be detected. Two major recurring clo nes were biased toward the use of TCRBJ1S5. Furthermore, T cell lines derived from Cure such infiltrated skin lesions and, enriched in TCRBV 14+ T cells, displayed HLA-class I-restricted lysis of the autologous melanoma cells. Clonal expansion of T cells was demonstrated in the T cell-infiltrated, postvaccine metastasis of a second patient as well. These results indicate that vaccination with autologous, DNP-modified melanoma cells can expand selected clones of T cells at the tumor site and that such clones are; potentially destructive to the tumor.