Cell surface receptor-targeted therapy of acute myeloid leukemia

A review

A. E. Frankel, E. L. Sievers, D. A. Scheinberg

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Combination chemotherapy produces remissions in patients with acute myeloid leukemia (AML). However, the majority of patients ultimately relapse and die with cytotoxic drug resistant blasts. Novel agents which circumvent resistance are needed. One such class are AML-cell surface targeted proteins. These genetically engineered polypeptides are hybrid molecules composed of two moieties-a haptophore which triggers AML cell binding and a toxophore which kills the cell. The haptophore or ligand portion consists of a monoclonal antibody or antibody fragment or a cytokine. These peptides react with cell surface receptors or antigens on AML cells. The haptophore is genetically or chemically linked to the toxophore. The toxophore may consist of an antibody Fc domain which triggers antibody-dependent cell cytotoxicity, a DNA-damaging cytotoxic drug, a radionuclide or a protein synthesis-inactivating peptide toxin. The toxophore may provide a cell death signal that overcomes standard resistance phenotypes. Further, the targeting provided by the haptophore may reduce normal tissue toxicities. This review describes some of the properties of the cell surface molecular targets, the reactive haptophores and toxophores and how these functional peptides have been optimally combined to kill leukemic blasts in patients with AML.

Original languageEnglish (US)
Pages (from-to)459-476
Number of pages18
JournalCancer Biotherapy and Radiopharmaceuticals
Volume15
Issue number5
StatePublished - 2000

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Cell Surface Receptors
Acute Myeloid Leukemia
Myeloid Cells
Peptides
Antibody-Dependent Cell Cytotoxicity
Therapeutics
Immunoglobulin Fragments
Surface Properties
Surface Antigens
Combination Drug Therapy
Radioisotopes
Pharmaceutical Preparations
Membrane Proteins
Cell Death
Monoclonal Antibodies
Cytokines
Ligands
Phenotype
Recurrence
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Cell surface receptor-targeted therapy of acute myeloid leukemia : A review. / Frankel, A. E.; Sievers, E. L.; Scheinberg, D. A.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 15, No. 5, 2000, p. 459-476.

Research output: Contribution to journalArticle

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