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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krag, D. N. Articles by Thomas, C. Search for Related Content PubMed PubMed Citation Articles by Krag, D. N. Articles by Thomas, C.

Selection of Tumor-binding Ligands in Cancer Patients with Phage Display Libraries

¹ Department of Surgery and Vermont Cancer Center, and ² Medical Biostatistics and Bioinformatics Facility, University of Vermont College of Medicine; Departments of ³ Surgical Pathology and ⁴ Hematology/Oncology, Fletcher Allen Health Care, Burlington, Vermont; and ⁵ Vermont Center for Cancer Medicine, Colchester, Vermont

Requests for reprints: David Krag, University of Vermont, Surgery, Given Building, E309 89 Beaumont Avenue, Burlington, VT 05405. Phone: 802-656-5830; Fax: 802-656-5833; E-mail: Girja.Shukla{at}uvm.edu.

Phage display has been used extensively in vitro and in animal models to generate ligands and to identify cancer-relevant targets. We report here the use of phage-display libraries in cancer patients to identify tumor-targeting ligands. Eight patients with stage IV cancer, including breast, melanoma, and pancreas, had phage-displayed random peptide or scFv library (1.6 x 10⁸-1 x 10¹¹ transducing units/kg) administered i.v.; tumors were excised after 30 minutes; and tumor-homing phage were recovered. In three patients, repeat panning was possible using phage recovered and amplified from that same patient's tumor. No serious side effects, including allergic reactions, were observed with up to three infusions. Patients developed antiphage antibodies that reached a submaximal level within the 10-day protocol window for serial phage administration. Tumor phage were recoverable from all the patients. Using a filter-based ELISA, several clones from a subset of the patients were identified that bound to a tumor from the same patient in which clones were recovered. The clone-binding to tumor was confirmed by immunostaining, bioassay, and real-time PCR–based methods. Binding studies with noncancer and cancer cell lines of the same histology showed specificity of the tumor-binding clones. Analysis of insert sequences of tumor-homing peptide clones showed several motifs, indicating nonrandom accumulation of clones in human tumors. This is the first reported series of cancer patients to receive phage library for serial panning of tumor targeting ligands. The lack of toxicity and the ability to recover clones with favorable characteristics are a first step for further research with this technology in cancer patients. (Cancer Res 2006; 66(15): 7724-33)

This article has been cited by other articles:

				Selection of Ligands in Cancer Patients with Phage Display Cancer Res., September 1, 2006; 66(17): 8925 - 8925. [Full Text] [PDF]