Neuroblastoma tumor cell-binding peptides identified through random peptide phage display

Zhang, Jianbing; Spring, Herbert; Schwab, Manfred

doi:10.1016/s0304-3835(01)00575-4

Cited by 112 publications

(87 citation statements)

References 26 publications

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“…In 2000, a report concluded that peptides isolated from phage display do not bind with high retention to tumors in vivo (43). Since then, a few studies have reported sequences from phage libraries that target neuroblastomas and prostate tumors in vivo; however, in these cases, the target antigens remain unknown (44,45). The successful imaging of ErbB-2 -expressing human breast carcinomas in SCID mice is a major step forward in developing cancer cell -associated imaging agents from phage display -selected peptides.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of an 111In-Radiolabeled Peptide as a Targeting and Imaging Agent for ErbB-2 Receptor–Expressing Breast Carcinomas

Kumar

Quinn

Deutscher

2007

Clinical Cancer Research

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Purpose: The cellular targeting and tumor imaging properties of a novel ErbB-2-avid peptide, discovered from bacteriophage display, were evaluated in human breast carcinoma cells and in breast carcinoma^xenografted mice. Experimental Design: The affinity of the ErbB-2 targeting peptide KCCYSL and its alanine substituted counterparts for the extracellular domain (ECD) of purified recombinant ErbB-2 (ErbB-2-ECD) was assessed by fluorescence titration. Binding of the KCCYSL peptide to breast and prostate carcinoma cells was analyzed by confocal microscopy. A DOTA(GSG)-KCCYSL peptide conjugate was radiolabeled with 111 In, and stability, target binding, and internalization were analyzed in vitro. In vivo biodistribution and single-photon emission computed tomography imaging studies were done with the radiolabeled peptide in MDA-MB-435 human breast tumorb earing severe combined immunodeficient mice. Results: KCCYSL peptide exhibited high affinity (295 F 56 nmol/L) to ErbB-2-ECD. Substitution of alanine for lysine, tryptophan, and cysteine reduced the peptide affinity f 1-to 2.4-fold, whereas replacing leucine completely abolished binding. Both biotin- KCCYSL and 111 In-DOTA(GSG)-KCCYSL were capable of binding ErbB-2^expressing human breast carcinoma cells in vitro. Approximately 11% of the total bound radioactivity was internalized in the carcinoma cells. Competitive binding studies indicated that the radiolabeled peptide exhibited an IC 50 value of 42.5 F 2.76 nmol/L for the breast carcinoma cells.

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Section: Discussionmentioning

confidence: 99%

Evaluation of an 111In-Radiolabeled Peptide as a Targeting and Imaging Agent for ErbB-2 Receptor–Expressing Breast Carcinomas

Kumar

Quinn

Deutscher

2007

Clinical Cancer Research

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“…This technique has been successfully used to identify affinity reagents for small molecules (10), nucleic acids (11), proteins (12,13), proteoliposomes (14,15), and inorganic materials (16). Phage display has proven powerful for use on whole cells (17,18) and tissues (19,20) because it allows targeting of transmembrane proteins in their native orientation and conformation with appropriate posttranslational modifications, and does not require a priori knowledge of the targets or their concentrations (21).…”

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confidence: 99%

Selection of phage-displayed peptides on live adherent cells in microfluidic channels

Wang

Teesalu

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Affinity reagents that bind to specific molecular targets are an essential tool for both diagnostics and targeted therapeutics. There is a particular need for advanced technologies for the generation of reagents that specifically target cell-surface markers, because transmembrane proteins are notoriously difficult to express in recombinant form. We have previously shown that microfluidics offers many advantages for generating affinity reagents against purified protein targets, and we have now significantly extended this approach to achieve successful in vitro selection of T7 phagedisplayed peptides that recognize markers expressed on live, adherent cells within a microfluidic channel. As a model, we have targeted neuropilin-1 (NRP-1), a membrane-bound receptor expressed at the surface of human prostate carcinoma cells that plays central roles in angiogenesis, cell migration, and invasion. We show that, compared to conventional biopanning methods, microfluidic selection enables more efficient discovery of peptides with higher affinity and specificity by providing controllable and reproducible means for applying stringent selection conditions against minimal amounts of target cells without loss. Using our microfluidic system, we isolate peptide sequences with superior binding affinity and specificity relative to the well known NRP-1-binding RPARPAR peptide. As such microfluidic systems can be used with a wide range of biocombinatorial libraries and tissue types, we believe that our method represents an effective approach toward efficient biomarker discovery from patient samples.

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“…A potential candidate peptide with promising targeting properties is the p160 peptide (14). The peptide p160 (VPWME-PAYQRFL), identified through random peptide phage display, is a linear dodecapeptide with specificity for the breast cancer cell line MDA-MB-435 and the neuroblastoma cell line WAC 2.…”

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confidence: 99%

Preclinical Evaluation of the Breast Cancer Cell-Binding Peptide, p160

Askoxylakis¹,

Zitzmann²,

Mier³

et al. 2005

Clinical Cancer Research

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Purpose: Selective delivery of drugs into the target tissue is expected to result in high drug concentrations in the tissue of interest and therefore enhanced drug efficacy. To develop a peptidebased radiopharmaceutical, we investigated the properties of a peptide with affinity for human breast cancer, which has been selected through phage display. Experimental Design: The bioactivity of the p160 peptide (VPWMEPAYQRFL) was evaluated in vitro and in vivo. The specific binding to human breast cancer MDA-MB-435 cells was confirmed in competition experiments. Internalization of the peptide was investigated with confocal microscopy. Furthermore, the biodistribution of 131 I-labeled p160 was studied in tumor-bearing mice. In vivo stability was evaluated at different periods after tracer administration using highperformance liquid chromatography analysis. Results: The binding of 125 I-labeled p160 was inhibited up to 95% by the unlabeled peptide with an IC 50 value of 0.6 Amol/L. In addition, 40% of the total bound activity was found to be internalized into the human breast cancer cells. Although a rapid degradation was seen, biodistribution studies in nude mice showed a higher uptake in tumor than in most of the organs. Perfusion of the animals caused a reduction of the radioligand accumulation in the healthy tissues, whereas the tumor uptake remained constant. A comparison of [

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Neuroblastoma tumor cell-binding peptides identified through random peptide phage display

Cited by 112 publications

References 26 publications

Evaluation of an 111In-Radiolabeled Peptide as a Targeting and Imaging Agent for ErbB-2 Receptor–Expressing Breast Carcinomas

Evaluation of an 111In-Radiolabeled Peptide as a Targeting and Imaging Agent for ErbB-2 Receptor–Expressing Breast Carcinomas

Selection of phage-displayed peptides on live adherent cells in microfluidic channels

Preclinical Evaluation of the Breast Cancer Cell-Binding Peptide, p160

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