Treatment of metastatic melanoma with autologous Melan-A/MART-1-specific cytotoxic T lymphocyte clones.

Immunotherapy by adoptive T-cell transfer aims at maximizing tumor antigen-specific T-cell responses. We treated 14 patients at the metastatic stage in a phase II study with Melan-A-specific T-cell clones generated from patient blood. During the period required for T-cell clone generation, the patients were treated by dacarbazine. Every patient received a T-cell clone suspension followed by subcutaneous injections of interleukin 2 and interferon alpha. Patients were monitored until disease progression occurred. We succeeded in obtaining autologous Melan-A-specific cytotoxic T lymphocyte clones, which were highly reactive against tumor cells for all the patients. Of the 14 patients treated, six (43%) experienced an objective response (CR + PR) with long-term complete remission for two patients (1 CR for 5 years and 1 CR for 28 months). Furthermore, we showed that all the clinical responses were significantly associated with in vivo expansion of the Melan-A-specific T-cell repertoire. This phenomenon appeared to be significantly associated with clinical responses. Thus, over the course of an adoptive cell transfer, monitoring this melanoma-specific T-cell expansion in patient blood appears crucial for predicting the clinical efficiency of such an immunological approach.