This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Marks, A. J. Articles by Wickremasinghe, R. G. Search for Related Content PubMed PubMed Citation Articles by Marks, A. J. Articles by Wickremasinghe, R. G.

Selective Apoptotic Killing of Malignant Hemopoietic Cells by Antibody-Targeted Delivery of an Amphipathic Peptide

¹ Department of Haematology, Royal Free and University College Medical School; ² Pharmacy Department, St. Bartholomew's Hospital, West Smithfield, London, United Kingdom; ³ Department of Haematology, Southampton University Hospitals Trust, Southampton, United Kingdom; and ⁴ Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom

Requests for reprints: R. Gitendra Wickremasinghe, Department of Hematology, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, United Kingdom. Phone: 44-7472-6198; Fax: 44-207-830-2092; E-mail: r.wickremasinghe{at}rfc.ucl.ac.uk..

The -helical amphipathic peptide D-(KLAKLAK)₂ is toxic to eukaryotic cells if internalized by a suitable targeting mechanism. We have targeted this peptide to malignant hemopoietic cells via conjugation to monoclonal antibodies, which recognize lineage-specific cell surface molecules. An anti-CD19/peptide conjugate efficiently killed 3/3 B lymphoid lines. However, an anti-CD33/peptide conjugate was cytotoxic to only one of three CD33-positive myeloid leukemia lines. The IC₅₀ towards susceptible lines were in the low nanomolar range. Conjugates were highly selective and did not kill cells that did not express the appropriate cell surface cognate of the antibody moiety. Anti-CD19/peptide conjugates efficiently killed cells from patients with chronic lymphocytic leukemia but anti-CD33/peptide reagents were less effective against fresh acute myeloid leukemia cells. We therefore suggest that amphipathic peptides may be of value as targeted therapeutic agents for the treatment of a subset of hematologic malignancies.

Key Words: leukemia • targeted therapy • immunotoxin • amphipathic peptide • apoptosis

This article has been cited by other articles:

				J. Zhong and Y. Chau Antitumor activity of a membrane lytic peptide cyclized with a linker sensitive to membrane type 1-matrix metalloproteinase Mol. Cancer Ther., September 1, 2008; 7(9): 2933 - 2940. [Abstract] [Full Text] [PDF]

				K. Rege, S. J. Patel, Z. Megeed, and M. L. Yarmush Amphipathic Peptide-Based Fusion Peptides and Immunoconjugates for the Targeted Ablation of Prostate Cancer Cells Cancer Res., July 1, 2007; 67(13): 6368 - 6375. [Abstract] [Full Text] [PDF]