Interleukin-4 Enhances the Survival of Severe Combined Immunodeficient Mice Engrafted With Human B-Cell Precursor Leukemia

• Published in: Blood 1996-06, Vol.87 (11), p.4797-4803
• Main Authors: Mitchell, Paul L.R., Clutterbuck, Robyn D., Powles, Ray L., De Lord, Corinne, Morilla, Ricardo, Hiorns, Lynne R., Titley, Jennifer, Catovsky, Daniel, Millar, John L.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Hematologic and hematopoietic diseases; Humans; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Interleukin-4 - pharmacology; Interleukin-4 - therapeutic use; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Mice; Mice, SCID; Neoplasm Transplantation; Neoplastic Stem Cells - drug effects; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Radiation Chimera; Severe Combined Immunodeficiency - complications; Transplantation, Heterologous
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V87.11.4797.bloodjournal87114797

Human interleukin-4 (hulL-4) has been shown to inhibit the growth in vitro of cells from patients with acute lymphoblastic leukemia (ALL). With the aim of determining whether this cytokine might be useful in the treatment of patients with ALL, the effects of hulL-4 on human B-cell precursor ALL engrafted in severe combined immunodeficient (SCID) mice were examined. The inhibition of [3H] thymidine uptake of primary ALL cells by hulL-4 was maintained following engraftment and passage of leukemia in SCID mice. Five of seven xenograft leukemias showed significant inhibition in vitro by hulL-4 at concentrations as low as 0.5 ng/mL; furthermore, hulL-4 counteracted the proliferative effects of IL-7. When used to treat two human leukemias engrafted in SCID mice, hulL-4 200 μg/kg/d, as a continuous 14-day subcutaneous infusion, suppressed the appearance of circulating lymphoblasts and extended survival of mice by 39% and 108%, respectively, the first demonstration of IL-4 activity against human leukemia in vivo. The mean steady-state hulL-4 level in mouse plasma during the infusion was 1.46 ng/mL (SEM ± 0.14 ng/mL), which was similar to concentrations found to be effective in vitro. ALL cells obtained from mice relapsing after hulL-4 treatment continued to show inhibition by the cytokine in vitro. These data suggest that IL-4 may be useful in the treatment of patients with ALL.