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

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...

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Bibliographic Details
Published in:European journal of cancer (1990) 2001-05, Vol.37 (7), p.892-902
Main Authors: Correale, P, Campoccia, G, Tsang, K.Y, Micheli, L, Cusi, M.G, Sabatino, M, Bruni, G, Sestini, S, Petrioli, R, Pozzessere, D, Marsili, S, Fanetti, G, Giorgi, G, Francini, G
Format: Article
Language:English
Subjects:
Aged
Antigen-Antibody Reactions - immunology
Antigen-specific immunoreactivity
Antineoplastic agents
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Dendritic cells
Dendritic Cells - immunology
Dose-Response Relationship, Drug
Female
Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use
hr-GM-CSF
hr-IL-2
Humans
Immunotherapy
Interleukin-2 - therapeutic use
Male
Medical sciences
Middle Aged
Neoplasms - drug therapy
Neoplasms - immunology
Pharmacology. Drug treatments
Phase Ib clinical trial
Recombinant Proteins - therapeutic use
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Summary: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 μg/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.
ISSN:0959-8049
1879-0852
DOI:10.1016/S0959-8049(01)00063-6