Safety evaluation of DT388IL3, a diphtheria toxin/interleukin 3 fusion protein, in the cynomolgus monkey

Cancer Immunology, Immunotherapy

Volumn 54, Issue 8, 2005, Pages 799-806

  Cohen, Kimberley A ^a   Liu, Tie Fu ^a   Cline, J Mark ^a   Wagner, Janice D ^a   Hall, Philip D ^b   Frankel, Arthur E ^a  

^a WAKE FOREST SCHOOL OF MEDICINE   (United States)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

AML; Cynomolgus monkey; Diphtheria toxin; DTIL3; Fusion protein

Indexed keywords

DIPHTHERIA TOXIN 388 INTERLEUKIN 3 FUSION PROTEIN; HYBRID PROTEIN; INTERLEUKIN 3 RECEPTOR; LIVER ENZYME; UNCLASSIFIED DRUG; DIPHTHERIA TOXIN; DIPHTHERIA TOXIN INTERLEUKIN 3 FUSION PROTEIN, RECOMBINANT; DIPHTHERIA TOXIN-INTERLEUKIN-3 FUSION PROTEIN, RECOMBINANT; INTERLEUKIN 3;

ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; ACUTE GRANULOCYTIC LEUKEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANOREXIA; ARTICLE; AUTOPSY; BLOOD CELL COUNT; BLOOD CHEMISTRY; BLOOD TESTIS BARRIER; BLOOD TOXICITY; CAUSE OF DEATH; CONTROLLED STUDY; CROSS REACTION; DISEASE SEVERITY; DOSE RESPONSE; DRUG HALF LIFE; DRUG INFUSION; DRUG SAFETY; DRUG TOLERABILITY; ENZYME BLOOD LEVEL; FEMALE; GASTROINTESTINAL TOXICITY; HISTOPATHOLOGY; HYPERPLASIA; LIVER TOXICITY; MACACA; MALAISE; MAXIMUM TOLERATED DOSE; METABOLIC DISORDER; NEPHROTOXICITY; NONHUMAN; ORGAN INJURY; PRIORITY JOURNAL; STATISTICAL SIGNIFICANCE; VASCULITIS; ANIMAL; CELL CULTURE; INTRAVENOUS DRUG ADMINISTRATION; PATHOLOGY;

ANIMALS; DIPHTHERIA TOXIN; FEMALE; INJECTIONS, INTRAVENOUS; INTERLEUKIN-3; LEUKEMIA, MYELOCYTIC, ACUTE; MACACA FASCICULARIS; MAXIMUM TOLERATED DOSE; RECOMBINANT FUSION PROTEINS; TUMOR CELLS, CULTURED;

EID: 22144433750     PISSN: 03407004     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00262-004-0643-4     Document Type: Article

References (32)

1. Ailles LE, Gerhard B, Hogge DE (1997) Detection and characterization of primitive malignant and normal progenitors in patients with acute myelogenous leukemia using long-term coculture with supportive feeder layers and cytokines. Blood 90:2555-2564
2. Alexander RL, Kucera GL, Klein B, Frankel AE (2000) In vitro interleukin-3 binding to leukemia cells predicts cytotoxicity of a diphtheria toxin/IL-3 fusion protein. Bioconjug Chem 11:564-568
3. Alexander RL, Ramage J, Kucera GL, Caligiuri MA, Frankel AE (2001) High affinity interleukin-3 receptor expression on blasts from patients with acute myelogenous leukemia correlates with cytotoxicity of a diphtheria toxin/IL-3 fusion protein. Leuk Res 25:875-881
4. Black JH, McCubrey JA, Willingham MC, Ramage J, Hogge DE, Frankel AE (2003) Diphtheria toxin-interleukin-3 fusion protein (DT(388)IL3) prolongs disease-free survival of leukemic immunocompromised mice. Leukemia 17:155-159
5. Bodley JW, Dunlop PC, VanNess BG (1984) Diphthamide in elongation factor 2: ADP-ribosylation, purification, and properties. Methods Enzymol 106:378-387
6. Brooke JS, Cha JH (2000) Molecular characterization of key diphtheria toxin:receptor interactions. Biochem Biophys Res Commun 275:374-381
7. Choe S, Bennett MJ, Fujii G, Curmi PM, Kantardjieff KA, Collier RJ, Eisenberg D (1992) The crystal structure of diphtheria toxin. Nature 357:216-222
8. Cohen KA, Liu T, Bissonette R, Puri RK, Frankel AE (2003) DAB389EGF fusion protein therapy of refractory glioblastoma multiforme. Curr Pharm Biotechnol 4:39-49
9. Cohen KA, Liu Cline JM, Wagner JD, Hall PD, Frankel AE (2004) Toxicology and pharmacokinetics of DT388IL3, a fusion toxin consisting of a truncated diphtheria toxin (DT388) linked to human interleukin 3 (IL3), in cynomolgus monkeys. Leuk Lymphoma 45:1647-1656
10. Feuring-Buske M, Frankel AE, Alexander RL, Gerhard B, Hogge DE (2002) A diphtheria toxin-interleukin 3 fusion protein is cytotoxic to primitive acute myeloid leukemia progenitors but spares normal progenitors. Cancer Res 62:1730-1736
11. Frankel AE, Fleming DR, Hall PD, Powell BL, Black JH, Leftwich C, Gartenhaus R (2003) A phase II study of DT fusion protein denileukin diftitox in patients with fludarabine-refractory chronic lymphocytic leukemia. Clin Cancer Res 9:3555-3561
12. Frankel AE, McCubrey JA, Miller MS, Delatte S, Ramage J, Kiser M, Kucera GL, Alexander RL, Beran M, Tagge EP, Kreitman RJ, Hogge DE (2000) Diphtheria toxin fused to human interleukin-3 is toxic to blasts from patients with myeloid leukemias. Leukemia 14:576-585
13. Frankel AE, Powell BL, Hall PD, Case LD, Kreitman RJ (2002) Phase I trial of a novel diphtheria toxin/granulocyte macrophage colony-stimulating factor fusion protein (DT388GMCSF) for refractory or relapsed acute myeloid leukemia. Clin Cancer Res 8:1004-1013
14. Frankel AE, Ramage J, Kiser M, Alexander R, Kucera G, Miller MS (2000) Characterization of diphtheria fusion proteins targeted to the human interleukin-3 receptor. Protein Eng 13:575-581
15. Hall PD, Virella G, Willoughby T, Atchley DH, Kreitman RJ, Frankel AE (2001) Antibody response to DT-GM, a novel fusion toxin consisting of a truncated diphtheria toxin (DT) linked to human granulocyte-macrophage colony stimulating factor (GM), during a phase I trial of patients with relapsed or refractory acute myeloid leukemia. Clin Immunol 100:191-197
16. Hotchkiss CE, Hall PD, Cline JM, Willingham MC, Kreitman RJ, Gardin J, Latimer A, Ramage J, Feely T, Delatte S, Tagge EP, Frankel AE (1999) Toxicology and pharmacokinetics of DTGM, a fusion toxin consisting of a truncated diphtheria toxin (DT388) linked to human granulocyte-macrophage colony-stimulating factor, in cynomolgus monkeys. Toxicol Appl Pharmacol 158:152-160
17. Kiser M, McCubrey JA, Steelman LS, Shelton JG, Ramage J, Alexander RL, Kucera GL, Pettenati M, Willingham MC, Miller MS, Frankel AE (2001) Oncogene-dependent engraftment of human myeloid leukemia cells in immunosuppressed mice. Leukemia 15:814-818
18. Liu TF, Urieto JO, Moore JE, Miller MS, Lowe AC, Thorburn A, Frankel AE (2004) Diphtheria toxin fused to variant interleukin-3 provides enhanced binding to the interleukin-3 receptor and more potent leukemia cell cytotoxicity. Exp Hematol 32:277-281
19. Misra D, Frankel AE, Hall PD, Liu TF, Black J, Moore JO (2004) The use of DT388IL3 fusion protein in patients with refractory acute myeloid leukemia (AML). Blood (in press)
20. Molnar I, Grover M, Frankel AE (2004) Fusion toxins in the treatment of cancer. Semin Oncol (in press
21. Nitsche A, Junghahn I, Thulke S (2003) Interleukin-3 promotes proliferation and differentiation of human hematopoietic stem cells but reduces their repopulation in NOD/SCID mice. Stem Cells 21:236-244
22. Redaelli A, Botteman MF, Stephens JM, Brandt S, Pashos CL (2004) Economic burden of acute myeloid leukemia: a literature review. Cancer Treat Rev 30:237-247
23. Schiffer CA (2001) Acute myeloid leukemia in adults: where do we go from here? Cancer Chemother Pharmacol 48(Suppl 1):S45-S52
24. Silverman JA, Mindell JA, Finkelstein A, Shen WH, Collier RJ (1994) Mutational analysis of the helical hairpin region of diphtheria toxin transmembrane domain. J Biol Chem 269:22524-22532
25. Smallshaw JE, Ghetie V, Rizo J, Fulmer JR, Trahan LL, Ghetie MA, Vitetta ES (2003) Genetic engineering of an immunotoxin to eliminate pulmonary vascular leak in mice. Nat Biotechnol 21:387-391
26. Suda T, Suda J, Ogawa M, Ihle JN (1985) Permissive role of interleukin 3 (IL-3) in proliferation and differentiation of multipotential hemopoietic progenitors in culture. J Cell Physiol 124:182-190
27. Uckun FM, Yanishevski Y, Tumer N, Waurzyniak B, Messinger Y, Chelstrom LM, Lisowski EA, Ek O, Zeren T, Wendorf H, Langue MC, Irvin JD, Myers DE, Fuller GB, Evans W, Gunther R (1997) Pharmacokinetic features, immunogenicity, and toxicity of B43(anti-CD19)-pokeweed antiviral protein immunotoxin in cynomolgus monkeys. Clin Cancer Res 3:325-337
28. van Gils FC, Budel LM, Burger H, van Leen RW, Lowenberg B, Wagemaker G (1994) Interleukin-3 (IL-3) receptors on rhesus monkey bone marrow cells: species specificity of human IL-3, binding characteristics, and lack of competition with GM-CSF. Exp Hematol 22:248-255
29. van Gils FC, Mulder AH, van den BC, Burger H, van Leen RW, Wagemaker G (1993) Acute side effects of homologous interleukin-3 in rhesus monkeys. Am J Pathol 143:1621-1633
30. vanderSpek JC, Murphy JR (2000) Fusion protein toxins based on diphtheria toxin: selective targeting of growth factor receptors of eukaryotic cells. Methods Enzymol 327:239-249
31. Wainwright MS, Rossi J, Schavocky J, Crawford S, Steinhorn D, Velentza AV, Zasadzki M, Shirinsky V, Jia Y, Haiech J, Van Eldik LJ, Watterson DM (2003) Protein kinase involved in lung injury susceptibility: evidence from enzyme isoform genetic knockout and in vivo inhibitor treatment. Proc Natl Acad Sci USA 100:6233-6238
32. Westcott MM, Abi-Habib RJ, Cohen KA, Willingham MC, Liu S, Bugge TH, Leppla SH, Frankel AE (2004) Diphtheria toxin-murine GMCSF-induced hepatoxicity is mediated by Kupffer cells. Mol Cancer Ther (in press)