title: Adoptive T cell therapy combined with intralesional administrations of TG1042 (adenovirus expressing interferon-γ) in metastatic melanoma patients.
abstract: 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.
authors.affiliation: Dermato-Oncology Department, Nantes Hospital, 1 Place Alexis Ricordeau, 44093, Nantes Cedex 1, France.
authors.forename: Amir
authors.initials: A
authors.lastname: Khammari
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Nguyen
authors.forename: Melanie
authors.initials: M
authors.lastname: Saint-Jean
authors.forename: Anne-Chantal
authors.initials: AC
authors.lastname: Knol
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Pandolfino
authors.forename: Gaelle
authors.initials: G
authors.lastname: Quereux
authors.forename: Anabelle
authors.initials: A
authors.lastname: Brocard
authors.forename: Lucie
authors.initials: L
authors.lastname: Peuvrel
authors.forename: Soraya
authors.initials: S
authors.lastname: Saiagh
authors.forename: Vincent
authors.initials: V
authors.lastname: Bataille
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Limacher
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dreno
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D064987:Cell- and Tissue-Based Therapy; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007371:Interferon-gamma / Q000235:genetics / Q000627:therapeutic use*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000637:transplantation*; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019139:Tumor Escape / Q000276:immunology
chemical_list: D008565:Membrane Proteins; D007371:Interferon-gamma; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
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