title: Recruitment of dendritic cells and enhanced antigen-specific immune reactivity in cancer patients treated with hr-GM-CSF (Molgramostim) and hr-IL-2. results from a phase Ib clinical trial.
abstract: Experimental findings suggest that granulocyte-monocyte-colony stimulating factor (GM-CSF) synergistically interacts with interleukin-2 (IL-2) in generating an efficient antigen-specific immune response. We evaluated the toxicity, antitumour activity and immunobiological effects of human recombinant (hr)-GM-CSF and hr-IL-2 in 25 cancer patients who subcutaneously (s.c.) received hr-GM-CSF 150 microg/day for 5 days, followed by hrIL-2 s.c. for 10 days and 15 days rest. Two of the most common side-effects were bone pain and fever. Of the 24 patients evaluable for response, 3 achieved partial remission, 13 experienced stable disease, and 8 progressed. Cytokine treatment increased the number of monocytes, dendritic cells (DC), and lymphocytes (memory T cells) in the peripheral blood and enhanced the antigen-specific immunoreactivity of these patients. Our results show that the hr-GM-CSF and hr-IL-2 combination is active and well tolerated. Its biological activity may support tumour associated antigen (TAA)-specific anticancer immunotherapy by increasing antigen presenting cell (APC) activity and T cell immune competence in vivo.
authors: Division of Medical Oncology, University of Siena, Viale Bracci 11, 53100, Siena, Italy.
authors: P
authors: P
authors: Correale
authors: G
authors: G
authors: Campoccia
authors: K Y
authors: KY
authors: Tsang
authors: L
authors: L
authors: Micheli
authors: M G
authors: MG
authors: Cusi
authors: M
authors: M
authors: Sabatino
authors: G
authors: G
authors: Bruni
authors: S
authors: S
authors: Sestini
authors: R
authors: R
authors: Petrioli
authors: D
authors: D
authors: Pozzessere
authors: S
authors: S
authors: Marsili
authors: G
authors: G
authors: Fanetti
authors: G
authors: G
authors: Giorgi
authors: G
authors: G
authors: Francini
mesh_terms: D000368:Aged; D000937:Antigen-Antibody Reactions / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C082430:molgramostim