Cytokines in tumor therapy. Interleukin-3.
IL-3 is a T-cell-derived hematopoietin. This cytokine stimulates the growth of multipotential progenitor cells and is therefore of clinical interest for the therapy of pancytopenic processes. Both in vitro and animal studies suggest that the development and maturation of multiple lineages of blood cells can best be achieved by combining IL-3 with other growth factors. IL-3 may therefore act to expand a primitive pool of precursor cells, and the presence of additional factors may aid in the differentiation of these cells to functional status. Studies of IL-3 in human beings are in early phase I stages. These trials indicate that this molecule has a short half-life, and hence should be given by routes that permit prolonged serum levels. IL-3 is generally well tolerated, and stimulation of progression to acute leukemia was not observed in our subjects with preleukemic states. This agent increased neutrophil, eosinophil, platelet, and reticulocyte counts in individual patients. However, responses varied from patient to patient, and the IL-3-induced changes in neutrophil counts were modest as opposed to those previously described after GM-CSF therapy. Comparison of the in vitro effects of IL-3 in the colony/culture assay to subsequent in vivo effects in a small number of patients indicates that increases in CFU-G, CFU-M, and CFU-GM can, at times, predict for changes in granulocyte and monocyte counts. A synthesis of currently available data indicates that future trials should be designed to treat additional patients with IL-3 alone and to combine IL-3 with GM-CSF, G-CSF, erythropoietin, and other growth factors.
Kurzrock
R
R
Department of Clinical Immunology and Biological Therapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Estrov
Z
Z
Talpaz
M
M
Gutterman
J U
JU
D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D004357:Drug Synergism; D006133:Growth Substances / Q000494:pharmacology; D006402:Hematologic Diseases / Q000628:therapy; D006801:Humans; D007377:Interleukin-3 / Q000493:pharmacokinetics / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology
D006133:Growth Substances; D007377:Interleukin-3; D011994:Recombinant Proteins