A recombinant fusion toxin targeted to the granulocyte-macrophage colony-stimulating factor receptor

Leukemia & Lymphoma
A E BendelJ P Perentesis

Abstract

Human granulocyte-macrophage colony stimulating factor (GMCSF) and its high affinity receptor function to regulate the proliferation and differentiation of myeloid lineage hematopoietic cells, and may participate in the pathogenesis of many malignant myeloid diseases. We have used genetic engineering based on the elucidated molecular structures of human granulocyte-macrophage colony-stimulating factor and diphtheria toxin (DT) to produce a recombinant fusion toxin, DTctGMCSF, that targets diphtheria toxin to high affinity GMCSF receptors expressed on the surface of blast cells from a large fraction of patients with acute myeloid leukemia (AML). DTctGMCSF was specifically immunoreactive with antidiphtheria toxin and anti-GMCSF antiseras, and exhibited the characteristic catalytic activity of diphtheria toxin, catalyzing the in vitro ADP-ribosylation of purified elongation factor 2. The cytotoxic effects of DTctGMCSF were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-tetrazolium (MTT) bromide assay of cell viability and in vivo assays of protein synthesis inhibition. DTctGMCSF were specifically cytotoxic to human leukemia cell lines bearing high affinity receptors for human GMCSF with IC50 of 10(-9) to 10(-11) M. It was not...Continue Reading

References

Sep 1, 1992·Blood Reviews·N H Russell
May 21, 1992·Nature·S ChoeD Eisenberg
Nov 22, 1991·Science·I Pastan, D FitzGerald
Nov 1, 1991·International Journal of Radiation Oncology, Biology, Physics·F M UckunC W Song
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J F Bazan
Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J P PerentesisJ R Murphy
Oct 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·K L HolmesJ N Ihle
Jun 5, 1987·Science·S C Clark, R Kamen
Aug 1, 1980·International Journal of Cancer. Journal International Du Cancer·S TsuchiyaK Tada
Jan 1, 1993·Cancer Treatment and Research·T G Woodworth, J C Nichols
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·M J BennettD Eisenberg

❮ Previous
Next ❯

Citations

Oct 26, 2001·Hematology/oncology Clinics of North America·J P Perentesis, E L Sievers
Jul 5, 2005·Expert Opinion on Investigational Drugs·R J Kreitman
Apr 7, 2006·Cell Biology and Toxicology·M Habibi RoudkenarS Bouzari

❮ Previous
Next ❯

Related Concepts

Related Feeds

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

CNS Lymphoma

In CNS lymphoma, cancerous cells from lymph tissues or other parts of the body form tumors in the brain and/or spinal cord. Here is the latest research on this rare non-Hodgkin lymphoma.