A Bispecific Recombinant Cytotoxin (DTEGF13) Targeting Human Interleukin-13 and Epidermal Growth Factor Receptors in a Mouse Xenograft Model of Prostate Cancer.

A Bispecific Recombinant Cytotoxin (DTEGF13) Targeting Human Interleukin-13 and Epidermal Growth Factor Receptors in a Mouse Xenograft Model of Prostate Cancer. Research Abstract Details 

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A Bispecific Recombinant Cytotoxin (DTEGF13) Targeting Human Interleukin-13 and Epidermal Growth Factor Receptors in a Mouse Xenograft Model of Prostate Cancer. Abstract Text:

Brad J Stish,Hua Chen,Yanqun Shu,Angela Panoskaltsis-Mortari,Daniel A Vallera,Brad J Stish,Hua Chen,Yanqun Shu,Angela Panoskaltsis-Mortari,Daniel A Vallera,Brad J Stish,Hua Chen,Yanqun Shu,Angela Panoskaltsis-Mortari,Daniel A Vallera,

PURPOSE: Overexpressed cytokine receptors are considered valid targets for new biologicals targeting prostate cancer. However, current reagents are limited in efficacy. Our goal was to determine the advantages of simultaneously targeting two established targets, epidermal growth factor receptor and interleukin-13 (IL-13) receptor, with a new bispecific cytotoxin in which both EGF and IL-13 cytokines were cloned onto the same single-chain molecule with truncated diphtheria toxin (DT(390)). EXPERIMENTAL DESIGN: In vitro experiments measured the potency of bispecific DTEGF13 and compared its activity to its monospecific counterparts, DTEGF and DTIL13. We determined whether the presence of both cytokine ligands on the same molecule was responsible for its superior activity. In vivo, DTEGF13 was given i.t. to athymic nude mice with established PC-3 human prostate cancer tumor xenografts on their flanks. RESULTS: In vitro, DTEGF13 was more potent than the monospecific cytotoxins against human prostate cancer lines. Enhanced activity was related to the presence of both cytokines on the same single-chain molecule and was not attributed to enhanced binding capacity. Killing was receptor specific. Cytotoxicity could be blocked with anti-EGF and anti-IL-13 antibodies. In vivo, DTEGF13, but not monospecific DTEGF or DTIL13, significantly inhibited the growth of established PC-3 tumors in nude mice (P < 0.0001). CONCLUSIONS: These data show for the first time that simultaneous targeting of cytokine receptors with two ligands on the same molecule has pronounced anticancer advantages. In an animal model in which human DTEGF13 is cross-reactive with mouse, DTEGF13 was highly effective in checking aggressive prostate tumor progression and was reasonably tolerated.

A Bispecific Recombinant Cytotoxin (DTEGF13) Targeting Human Interleukin-13 and Epidermal Growth Factor Receptors in a Mouse Xenograft Model of Prostate Cancer. Publishing Authors By Initials

BJ Stish,H Chen,Y Shu,A Panoskaltsis-Mortari,DA Vallera,BJ Stish,H Chen,Y Shu,A Panoskaltsis-Mortari,DA Vallera,BJ Stish,H Chen,Y Shu,A Panoskaltsis-Mortari,DA Vallera,

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A Bispecific Recombinant Cytotoxin (DTEGF13) Targeting Human Interleukin-13 and Epidermal Growth Factor Receptors in a Mouse Xenograft Model of Prostate Cancer. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Clinical cancer research : an official journal of

VOLUME: 13

Page Numbers: 6486-93

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 1

MONTH: Nov

YEAR: 2007

A Bispecific Recombinant Cytotoxin (DTEGF13) Targeting Human Interleukin-13 and Epidermal Growth Factor Receptors in a Mouse Xenograft Model of Prostate Cancer. Information

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LANGUAGE: eng

NlmUniqueID: 9502500

A Bispecific Recombinant Cytotoxin (DTEGF13) Targeting Human Interleukin-13 and Epidermal Growth Factor Receptors in a Mouse Xenograft Model of Prostate Cancer. Keywords Mesh Terms:

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AFFILIATION: Authors' Affiliations: Departments of Therapeutic Radiology-Radiation Oncology and Pediatrics, Section on Molecular Cancer Therapeutics, University of Minnesota Cancer Center, Minneapolis, Minnesota.

Country: United States

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MEDLINETA: Clin Cancer Res

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