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Treatment of Metastatic Melanoma with Autologous Melan-A/Mart-1-Specific Cytotoxic T Lymphocyte Clones

Abstract : 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 þ 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.
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Submitted on : Monday, February 17, 2020 - 5:32:15 PM
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Amir Khammari, Nathalie Labarrière, Virginie Vignard, Jean-Michel Nguyen, Marie-Christine Pandolfino, et al.. Treatment of Metastatic Melanoma with Autologous Melan-A/Mart-1-Specific Cytotoxic T Lymphocyte Clones. Journal of Investigative Dermatology, Nature Publishing Group, 2009, 129 (12), pp.2835 - 2842. ⟨10.1038/jid.2009.144⟩. ⟨inserm-02481977⟩

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