Abstract
The functionally related haematoproteins granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3) exhibit overlapping but complementary haematopoietic effects, providing a clinical rationale for their potential use in combination. The discovery of a receptor on haematopoietic progenitor cells capable of binding both GM-CSF and IL-3 provided a scientific rationale for development of a GM-CSF/IL-3 fusion protein, PIXY321, with the potential for enhanced biologic effects via cross linking receptor binding. PIXY321 binds to cell lines expressing specific receptors for either ligand, and exhibits enhanced biologic activity in human haematopoietic progenitor cell assays. In preclinical studies, it accelerated neutrophil and platelet recovery in rhesus monkeys subjected to sublethal irradiation. Based on its preclinical profile, PIXY321 is being evaluated in clinical trials for its therapeutic potential to ameliorate treatment- or disease related haematopoietic suppression. Results of phase I/II trials suggest that PIXY321 can stimulate multilineage haematopoiesis in vivo and enhance neutrophil and platelet recovery following chemotherapy and bone marrow transplantation. Clinical trials are continuing to determine optimal dose levels and to more fully evaluate the effects of the fusion protein in a variety of settings. PIXY321 generally has been well tolerated; the most frequent adverse event is local reaction at the injection site. Adverse events including constitutional symptoms are generally mild and reversible. Early clinical results suggest that PIXY321 elicits the biologic effects of its component cytokines and thus represents a novel means of delivering two independent but interactive cytokines in combination.
Original language | English (US) |
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Pages (from-to) | 110-118 |
Number of pages | 9 |
Journal | FORUM - Trends in Experimental and Clinical Medicine |
Volume | 5 |
Issue number | 2 |
State | Published - 1995 |
Keywords
- Cytokines
- Growth factors
- Haematopoietins
- PIXY321
ASJC Scopus subject areas
- General Medicine