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

• Published in: European journal of cancer (1990) Vol. 37; no. 7; pp. 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: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.05.2001; Elsevier
• 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; Antigen-specific immunoreactivity; Phase Ib clinical trial; hr-GM-CSF; Dendritic cells; Immunotherapy; hr-IL-2; Human; Dendritic cell; Carcinoma; Tumor associated antigen; Sarcoma; Cytokine; Malignant tumor; Treatment; Interleukin 2; Polypeptide; Phase I trial; Adult; Advanced stage; Granulocyte macrophage colony stimulating factor
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(01)00063-6

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.