This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Donev, R. M. Articles by Morgan, B. P. PubMed PubMed Citation Articles by Donev, R. M. Articles by Morgan, B. P.

Modulation of CD59 Expression by Restrictive Silencer Factor–Derived Peptides in Cancer Immunotherapy for Neuroblastoma

Departments of ¹ Medical Biochemistry and Immunology and ² Pharmacology, Therapeutics and Toxicology, School of Medicine, Cardiff University, Cardiff, United Kingdom

Requests for reprints: Rossen M. Donev, Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University Heath Park, Cardiff CF14 4XN, United Kingdom. Phone: 44-029-206-87868; Fax: 44-029-206-87079; E-mail: donevrm{at}cardiff.ac.uk.

Key Words: CD59 • complement killing • neuroblastoma • REST • therapeutic peptides

Tumor cells escape clearance by complement by abundantly expressing CD59 and other membrane complement regulators. Existing strategies for blocking/knocking down these regulators can contribute to tumor immunoclearance in vitro; however, there are numerous difficulties restricting their use in vivo. Here, we report a new strategy for suppression of CD59 expression in neuroblastoma using peptides that target regulators of CD59 expression. We identified the neural-restrictive silencer factor (REST) as a target for modulation of CD59 expression in neuroblastoma. We next designed plasmids that encoded peptides comprising different DNA-binding domains of REST and transfected them into neuroblastoma cell lines. These peptides suppressed CD59 expression, sensitizing neuroblastoma to complement-mediated killing triggered by anti-GD2 therapeutic monoclonal antibody. These CD59-modulating peptides might be effective therapeutic adjuvants to therapeutic monoclonal antibodies used for treatment of neuroblastoma and other cancer types sharing the same mechanism for regulation of CD59 expression. [Cancer Res 2008;68(14):5979–87]