Phage-displayed random peptide libraries in mice: toxicity after serial panning

Krag, David N.; Fuller, Susan P.; Oligino, Lyn; Pero, Stephanie C.; Weaver, Donald L.; Soden, Amy L.; Hébert, Caroline; Mills, Sadie; Liu, Chen; Peterson, Daniel L.

doi:10.1007/s00280-002-0489-4

Cited by 23 publications

(23 citation statements)

References 48 publications

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“…The complexities of the random 12-and 20-mer libraries were 1.26 Â 10 7 and 1.8 Â 10 7 different peptides, respectively. The details of library preparation, titration, elution of cell-bound phage, phage plating, and amplification have been described in detail in our earlier publications (19,32,34,35).…”

Section: Phage Librariesmentioning

confidence: 99%

“…This was carried out using an ELISA-based method developed and used in our preclinical study (32). Briefly, a 96-well polystyrene microplate (F96 Maxisorb Immuno plate, Nulge Nunc, Roskilde, Denmark) was coated with 1 Â 10 7 transducing units (TU) of filamentous phage ( from phage library) overnight at 4jC.…”

Section: Estimation Of Serum Phage Antibodiesmentioning

confidence: 99%

“…The rinsed tissue and cells were homogenized to release cell-internalized phage. The bacterial host infection, plating, titration, and amplification were done by the methods as described earlier for peptide (19,32,34,35) and scFv (36,37) libraries. Phage administration, tumor harvest, and amplification were repeated twice for a maximum of three infusions.…”

Section: Tumor Processing and Phage Recoverymentioning

confidence: 99%

“…Our experimental studies in mice provided the necessary preclinical information for conducting serial PDL infusions (32). We now report here a first set of cancer patients that have participated in a phase I study and have received PDL infusions.…”

Section: Introductionmentioning

confidence: 99%

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

Krag

Shukla²,

Shen³

et al. 2006

Cancer Research

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187

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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 Â 10 8 -1 Â 10 11 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)

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Section: Phage Librariesmentioning

confidence: 99%

Section: Estimation Of Serum Phage Antibodiesmentioning

confidence: 99%

Section: Tumor Processing and Phage Recoverymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Krag

Shukla²,

Shen³

et al. 2006

Cancer Research

Self Cite

187

145

View full text Add to dashboard Cite

show abstract

“…After demonstrating minimal toxicity during in vivo screening of phage-displayed peptide libraries in mice, another group received FDA approval for the use of the technique in human clinical trials [74]. Krag et al reported the results of a Phase I clinical trial in 2006 in which eight stage IV cancer patients received intravenous infusions of filamentous phage-displayed peptide or single-chain antibody libraries [75].…”

Section: Potential Target-specific Peptides Identified Using Phage-dimentioning

confidence: 99%

Potential of phage-displayed peptide library technology to identify functional targeting peptides

Krumpe

Mori²

2007

Expert Opinion on Drug Discovery

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Combinatorial peptide library technology is a valuable resource for drug discovery and development. Several peptide drugs developed through phage-displayed peptide library technology are presently in clinical trials and the authors envision that phage-displayed peptide library technology will assist in the discovery and development of many more. This review attempts to compile and summarize recent literature on targeting peptides developed through peptide library technology, with special emphasis on novel peptides with targeting capacity evaluated in vivo.

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Bacteriophage Therapies Targets Multiple Diseases Caused by Protein Misfolding

Solomon

2020

Biocommunication of Phages

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Phage-displayed random peptide libraries in mice: toxicity after serial panning

Abstract: Serial administration of an RPL is well tolerated and serial panning in individual mice leading to consensus sequence motifs is possible. Based on these preclinical data the Food and Drug Administration has approved the implementation of human clinical trials with this technique.

Cited by 23 publications

References 48 publications

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

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

Potential of phage-displayed peptide library technology to identify functional targeting peptides

Bacteriophage Therapies Targets Multiple Diseases Caused by Protein Misfolding

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