Steps toward mapping the human vasculature by phage display

Arap, Wadih; Kolonin, Mikhail G.; Trepel, Martin; Lahdenranta, Johanna; Cardó-Vila, Marina; Giordano, Ricardo J.; Mintz, Paul J.; Ardelt, Peter; Yao, Virginia J.; Vidal, Claudia I.; Chen, Limor; Flamm, Anne L.; Valtanen, Heli; Weavind, Lisa; Hicks, Marshall E.; Pollock, Raphael E.; Botz, Gregory H.; Bucana, Corazon D.; Koivunen, Erkki; Cahill, Dolores J.; Troncoso, Patricia; Baggerly, Keith A.; Pentz, Rebecca D.; Anh, Kim; Logothetis, Christopher J.; Pasqualini, Renata

doi:10.1038/nm0202-121

Cited by 534 publications

(513 citation statements)

References 28 publications

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“…11e13 Among these, the cyclic peptide motif CGRRAGGSC (single letter code) was validated as a mimic of IL-11, mapping to a previously unrecognized binding site that interacts with IL-11 receptor (IL-11R) with consequent STAT-3 phosphorylation and cell proliferation. 14,15 In addition to our previous work demonstrating elevated levels of IL-11R in prostate cancer, 11 similar data have been reported in carcinomas of the breast, colon, and stomach; bone sarcomas; and leukemia/lymphomas. 16e20 In preclinical models, the CGRRAGGSC peptide conjugated to a proapoptotic moiety (CGRRAGGSC-GG-D [KLAKLAK] 2 ) selectively targeted prostate cancer osteoblastic metastasis, as well as osteosarcoma metastasis in the lung, while having no toxic effect on normal surrounding tissues.…”

supporting

confidence: 84%

Interleukin-11 Receptor Is a Candidate Target for Ligand-Directed Therapy in Lung Cancer

Cardó-Vila

Marchiò

Sato

et al. 2016

The American Journal of Pathology

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We previously isolated an IL-11emimic motif (CGRRAGGSC) that binds to IL-11 receptor (IL-11R) in vitro and accumulates in IL-11Reexpressing tumors in vivo. This synthetic peptide ligand was used as a tumortargeting moiety in the rational design of BMTP-11, which is a drug candidate in clinical trials. Here, we investigated the specificity and accessibility of IL-11R as a target and the efficacy of BMTP-11 as a ligandtargeted drug in lung cancer. We observed high IL-11R expression levels in a large cohort of patients (n Z 368). In matching surgical specimens (i.e., paired tumors and nonmalignant tissues), the cytoplasmic levels of IL-11R in tumor areas were significantly higher than in nonmalignant tissues (n Z 36; P Z 0.003). Notably, marked overexpression of IL-11R was observed in both tumor epithelial and vascular endothelial cell membranes (n Z 301; P < 0.0001). BMTP-11 induced in vitro cell death in a representative panel of human lung cancer cell lines. BMTP-11 treatment attenuated the growth of subcutaneous xenografts and reduced the number of pulmonary tumors after tail vein injection of human lung cancer cells in mice. Our findings validate BMTP-11 as a pharmacologic candidate drug in preclinical models of lung cancer and patient-derived tumors. Moreover, the high expression level in patients with non-small cell lung cancer is a promising feature for potential translational applications. (Am J Pathol 2016, 186: 2162e2170; http://dx

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supporting

confidence: 84%

Interleukin-11 Receptor Is a Candidate Target for Ligand-Directed Therapy in Lung Cancer

Cardó-Vila

Marchiò

Sato

et al. 2016

The American Journal of Pathology

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“…17 This strategy revealed vascular-specific ligands, which allowed experimental tissuespecific targeting of tumor blood vessels 18 as well as normal blood vessels to create a molecular map of the human vasculature. [19][20][21] It has been demonstrated that the ligands carrying an RGD-4C motif sequence (CDCRGDCFC) can be internalized by cells that express av integrins through receptor-mediated endocytosis. Only targeted AAVP constructs that display an RGD-4C motif in their major coat protein subunit bind to cells and are internalized efficiently, whereas constructs with scrambled or mutated motifs are not.…”

Section: Discussionmentioning

confidence: 99%

Tumor vasculature‐targeted delivery of tumor necrosis factor‐α*

Tandle

Hanna

Lorang

et al. 2008

Cancer

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BACKGROUND: Recently, considerable efforts have been directed toward antivascular therapy as a new modality to treat human cancers. However, targeting a therapeutic gene of interest to the tumor vasculature with minimal toxicity to other tissues remains the objective of antivascular gene therapy. Tumor necrosis factor‐α (TNF‐α) is a potent antivascular agent but has limited clinical utility because of significant systemic toxicity. At the maximum tolerated doses of systemic TNF‐α, there is no meaningful antitumor activity. Hence, the objective of this study was to deliver TNF‐α targeted to tumor vasculature by systemic delivery to examine its antitumor activity. METHODS: A hybrid adeno‐associated virus phage vector (AAVP) was used that targets tumor endothelium to express TNF‐α (AAVP‐TNF‐α). The activity of AAVP‐TNF‐α was analyzed in various in vitro and in vivo settings using a human melanoma tumor model. RESULTS: In vitro, AAVP‐TNF‐α infection of human melanoma cells resulted in high levels of TNF‐α expression. Systemic administration of targeted AAVP‐TNF‐α to melanoma xenografts in mice produced the specific delivery of virus to tumor vasculature. In contrast, the nontargeted vector did not target to tumor vasculature. Targeted AAVP delivery resulted in expression of TNF‐α, induction of apoptosis in tumor vessels, and significant inhibition of tumor growth. No systemic toxicity to normal organs was observed. CONCLUSIONS: Targeted AAVP vectors can be used to deliver TNF‐α specifically to tumor vasculature, potentially reducing its systemic toxicity. Because TNF‐α is a promising antivascular agent that currently is limited by its toxicity, the current results suggest the potential for clinical translation of this strategy. Cancer 2009. Published 2008 by the American Cancer Society.

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“…The development of bacteriophage display-selected peptide-based imaging agents has centered primarily on the vascular endothelial component, a v b 3 -integrin, targeting RGD peptide or its derivatives (38)(39)(40). Few other bacteriophage-selected peptides that bind tumor-associated antigens have been reported to function as efficacious tumor imaging agents in vivo.…”

Section: Discussionmentioning

confidence: 99%

¹¹¹In-Labeled Galectin-3–Targeting Peptide as a SPECT Agent for Imaging Breast Tumors

Kumar¹,

Deutscher²

2008

J Nucl Med

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Steps toward mapping the human vasculature by phage display

Cited by 534 publications

References 28 publications

Interleukin-11 Receptor Is a Candidate Target for Ligand-Directed Therapy in Lung Cancer

Interleukin-11 Receptor Is a Candidate Target for Ligand-Directed Therapy in Lung Cancer

Tumor vasculature‐targeted delivery of tumor necrosis factor‐α*

¹¹¹In-Labeled Galectin-3–Targeting Peptide as a SPECT Agent for Imaging Breast Tumors

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Steps toward mapping the human vasculature by phage display

Cited by 534 publications

References 28 publications

Interleukin-11 Receptor Is a Candidate Target for Ligand-Directed Therapy in Lung Cancer

Interleukin-11 Receptor Is a Candidate Target for Ligand-Directed Therapy in Lung Cancer

Tumor vasculature‐targeted delivery of tumor necrosis factor‐α*

111In-Labeled Galectin-3–Targeting Peptide as a SPECT Agent for Imaging Breast Tumors

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¹¹¹In-Labeled Galectin-3–Targeting Peptide as a SPECT Agent for Imaging Breast Tumors