Adoptive T cell therapy combined with intralesional administrations of TG1042 (adenovirus expressing interferon-γ) in metastatic melanoma patients
| Autor: | Brigitte Dréno, Lucie Peuvrel, Vincent Bataille, Gaëlle Quéreux, Mélanie Saint-Jean, Amir Khammari, Soraya Saiagh, Anabelle Brocard, Jean-Marc Limacher, Anne-Chantal Knol, Marie-Christine Pandolfino, Jean-Michel Nguyen |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Proto-Oncogene Proteins B-raf Cancer Research medicine.medical_treatment T cell Immunology Cell- and Tissue-Based Therapy medicine.disease_cause Immunotherapy Adoptive Adenoviridae GTP Phosphohydrolases Immune tolerance Interferon-gamma Lymphocytes Tumor-Infiltrating Immune system Cell Line Tumor medicine Humans Immunology and Allergy Interferon gamma Melanoma Aged business.industry Membrane Proteins Genetic Therapy Immunotherapy Middle Aged medicine.disease Combined Modality Therapy medicine.anatomical_structure Oncology Tumor Escape Cancer research Female business medicine.drug |
| Zdroj: | Cancer Immunology, Immunotherapy. 64:805-815 |
| ISSN: | 1432-0851 0340-7004 |
| Popis: | Tumor immune escape has recently been shown to be related to the development of an immune tolerance state of the microenvironment. Cytokines activating the immune system such as IFN-γ can be used to reverse the immune escape and thus to potentiate the efficacy of immunotherapy. A clinical study was conducted in 18 stage IIIc/IV melanoma patients treated with tumor-infiltrating lymphocytes (TILs) in combination with intratumoral TG1042 injection (adenovirus expressing IFN-γ). The primary objective was to investigate the safety of treatment. Secondary objectives were to study the clinical response and translational research. The treatment was well tolerated. Among the 13 patients evaluable for tumor response, 38.5 % had an overall objective response (OOR = CR + PR) and disease control rate (DCR = CR + PR + S) of 46 %. The clinical response of the 37 targeted lesions led to an OOR of 51 % and a DCR of 75 %. Translational research on predictive markers did not significantly differ between responder and non-responder patients. However, specifically regarding injected lesions, the clinical response correlated with CD3−/CD56+ NK cells which could be activated by TG1042. Further larger studies of this combined immunotherapy are needed to confirm our findings. Intralesional TG1042 combined with antigen-selected TILs should be discussed. |
| Databáze: | OpenAIRE |
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