title: Anti-tumor properties of human-activated macrophages produced in large scale for clinical application.
abstract: When properly activated, macrophages can be tumoricidal. To harness the therapeutic potential of these cells, we have developed a process for ex vivo production of large numbers of IFN-gamma-activated monocyte-derived macrophages. These monocyte-derived activated killer (MAK) cells have been safely administered to cancer patients with minimal residual disease in phase I/II clinical studies. To evaluate efficacy of treatment with MAK cells, phase III clinical studies are necessary. The process of MAK cell production has been further optimized and qualified for use in large cohorts of patients. In this study, we characterized MAK cells produced in large scale by studying their phenotype and functions. MAK cells were shown to exert anti-tumor activity by killing tumor cells and inhibiting their proliferation. These activities were enhanced by activation with IFN-gamma and addition of anti-tumor antibodies. Tumor necrosis factor-alpha (TNF-alpha) was one of the mediators used by MAK cells to inhibit tumor proliferation. To facilitate logistics of clinical trials, a process for MAK cell cryopreservation has been developed. We verified in vitro that cryopreserved cells retained the activity of fresh cells and were stable during storage. The safety and efficacy of cryopreserved MAK cells (Bexidem) are currently being assessed on superficial bladder cancer patients in a phase II/III clinical trial.
authors.affiliation: IDM Research Laboratory, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Baron-Bodo
authors.forename: Paula
authors.initials: P
authors.lastname: Doceur
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Lefebvre
authors.forename: Karine
authors.initials: K
authors.lastname: Labroquère
authors.forename: Catherine
authors.initials: C
authors.lastname: Defaye
authors.forename: Christophe
authors.initials: C
authors.lastname: Cambouris
authors.forename: Didier
authors.initials: D
authors.lastname: Prigent
authors.forename: Margarita
authors.initials: M
authors.lastname: Salcedo
authors.forename: Aurélie
authors.initials: A
authors.lastname: Boyer
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nardin
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D015925:Cryopreservation; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma