title: Immunotoxin therapy of hematologic malignancies.
abstract: Patients with chemotherapy relapsed or refractory hematologic malignancies may be effectively treated with allogeneic or autologous stem cell transplants. However, many patients cannot be transplanted due to age, comorbidities, or lack of suitable donors. Further, a fraction of patients relapse post-transplant. Novel therapeutic agents that can kill multidrug-resistant malignant stem cells and are not myelosuppressive are needed. One class of such agents is immunotoxins. Immunotoxins consist of cell-selective ligands covalently linked to peptide toxins. The ligand delivers the molecule to specific cell surface receptors on malignant cells. The toxin triggers cell death either by reaching the cytosol and catalytically inactivating vital cell processes or by modifying the tumor cell surface membrane. We have synthesized immunotoxins for therapy of chemoresistant hematologic diseases. In this review, we will detail the synthesis of a number of these drugs and describe their preclinical and clinical activity. Several of these agents have shown dramatic antitumor effects in patients with hematologic neoplasms, and one immunotoxin has been approved for use by the US Food and Drug Administration (FDA). Over the next several decades, a growing number of these agents should reach the clinic.
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Frankel
authors.forename: David M
authors.initials: DM
authors.lastname: Neville
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bugge
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kreitman
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Leppla
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016923:Cell Death / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D019008:Drug Resistance, Neoplasm; D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D011956:Receptors, Cell Surface / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D000922:Immunotoxins; D011956:Receptors, Cell Surface