Targeted Toxins
- Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157 [A. E. F.], and Laboratory of Molecular Biology [R. J. K.] and Developmental Therapeutics Program, Clinical Trials Unit, Medicine Branch [E. A. S.], National Cancer Institute, NIH, Bethesda, Maryland 20892-7458
Abstract
Targeted toxins, consisting of tumor-selective ligands coupled to polypeptide toxins, represent a new class of cancer therapeutics that kills malignant cells by inactivating cytosolic protein synthesis and inducing apoptosis. A number of these molecules have been produced under good manufacturing practice conditions and given systemically to patients with a variety of neoplasms. The promising results to date and the remaining pharmacological hurdles are discussed.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 To whom requests for reprints should be addressed, at Wake Forest University School of Medicine, Hanes 4046, Medical Center Drive, Winston Salem, NC 27157. Phone: (914) 642-3075; E-mail: AFrankel{at}WFUBMC.edu
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↵2 The abbreviations used are: DT, diphtheria toxin; PE, Pseudomonas exotoxin; RTA, ricin toxin A; bR, blocked ricin; Gel, gelonin; PAP, pokeweed antiviral protein; IL, interleukin; dgA, deglycosylated ricin A chain; HCL, hairy cell leukemia; CTCL, cutaneous T-cell lymphoma; CLL, chronic lymphocytic leukemia; HD, Hodgkin’s disease; ATL, acute T-cell leukemia; Tf, transferrin; DTGM, —; GM-CSF, granulocyte/macrophage-colony stimulating factor; MRI, magnetic resonance imaging; VLS, vascular leak syndrome; Mab, monoclonal antibody.
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↵3 E. Olsen, M. Duvic, A. Frankel, Y. Kim, A. Martin, E. Vonderheid, B. Jegasothy, G. Wood, M. Gordon, P. Heald, A. Oseroff, L. Pinter-Brown, G. Bowen, T. Kuzel, D. Fivenson, F. Foss, M. Glode, A. Molina, E. Knobler, S. Stewart, K. Cooper, S. Stevens, F. Craig, J. Reuben, P. Bacha, and J. Nichols. Pivotal Phase III trial of two dose levels of DAB389IL2 (ONTAK) for the treatment of cutaneous T-cell lymphoma, submitted for publication.
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↵4 E. Sausville and R. Messman, unpublished observations.
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↵5 L. H. Pai-Scherf, D. Pearson, R. Wittes, M. C. Willingham, and I. Pastan. A Phase I study of LMB-7,[ B3(Fv)PE38], a recombinant single-chain immunotoxin for advanced solid tumors, submitted for publication.
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- Accepted November 4, 1999.
- Received October 4, 1999.
- Revision received November 4, 1999.
