Growth factor complex

A growth factor, protein complex technology, applied in the field of regulating cell proliferation and/or migration, growth factor complex, can solve the problem of low IGF affinity

Inactive Publication Date: 2004-10-27
FACTOR THERAPEUTICS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These substances bind IGF wi

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0179] Example 1: Competition binding assay to determine the ability of insulin, pro-IGF-II and IGF-I to compete with IGF-II for vitronectin binding

[0180] Due to the structural similarity between IGF and insulin, the binding of insulin to vitronectin was tested. Cross-linking experiments performed by Upton et al., 1999 (supra) showed that insulin is unlikely to compete with IGF-II for binding to vitronectin, as was the case with IGF-I. Therefore, high concentrations of insulin were tested to determine whether insulin could compete with radiolabeled IGF-II for vitronectin binding. shown in figure 1 The results showed that insulin was hardly related to [ 125 I]-IGF-II competes for vitronectin binding.

[0181] Studies of IGF-I as a competitor of IGF-II binding to vitronectin suggest that IGF-I can compete[ 125 I]-IGF-II combined with vitronectin ( figure 2 ). However, IGF-I was significantly less potent than IGF-II in competing with radiolabeled IGF-II for vitronectin ...

Embodiment 2

[0183] Example 2: Study of PAI-1 and uPAR as Competitors for IGF-II Binding to Vitronectin

[0184] PAI-1 and suPAR were investigated as possible molecules that compete with IGF-II for vitronectin binding, since these proteins have been reported to bind vitronectin (Declerck et al., 1988, J. Biol. Chem. 263 15454; Wei et al., 1994, Biol. Chem. Journal 269 32380; Kanse et al., 1996, Exp. Cell Res. 224 344). At concentrations up to 2000nM, PAI-1 was observed to interact with [ 125 I]-IGF-II competes for vitronectin IC binding 50 The value is about 524nM ( Figure 4 ). Although from IC 50This concentration appears to be relatively high, but such concentrations have been found to be relevant to tumors in vivo (Grondahl-Hansen et al., 1993, Cancer Research 53 2513). In fact, Kjoller et al., 1997, Exp. Cell Res. 232 420, found that 370 nM of PAI-1 was required to achieve a half-maximal effect in an assay determining the ability of PAI-1 to inhibit migration of WISH cells. This...

Embodiment 3

[0189] Example 3: Binding of IGF-I and IGF-II to vitronectin in the presence of non-glycosylated recombinant IGFBP-3

[0190] To investigate whether IGFBP could mediate the binding of IGF to vitronectin, increasing concentrations of IGFBP-3 in the presence of [ 125 I]-IGF-I or [ 125 I]-IGF-II in the case of the role. The results are shown in Figure 5 .

[0191] At the concentrations tested, 10 ng / well of IGFBP-3 resulted in the greatest amount of [ 125 I]-IGF-I bound to vitronectin-coated wells, while 30ng / well of IGFBP-3 resulted in the greatest amount of [ 125 I]-IGF-II binds to vitronectin-coated wells. Said role in [ 125 This is most evident in the case of I]-IGF-I, as low counts of [ 125 I]-IGF-I bound vitronectin, and even at the lowest concentration of IGFBP-3 (3.7ng), this binding was increased ( Figure 5 A). on the contrary,[ 125 I]-IGF-II did not show the increase in binding obtained on vitronectin-coated wells up to a concentration of 11 ng / 100 μL-33 ng / ...

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Abstract

An isolated protein complex is provided which includes a growth factor, growth factor binding protein and vitronectin. Preferably, the isolated protein complex includes an insulin-like growth factor-I, insulin-like growth factor binding protein-3 or insulin-like growth factor binding protein-5 and vitronectin. Also provided are methods of modulating cell proliferation and/or migration by administering said protein complex for the purposes of wound healing, skin repair and tissue replacement therapy. Conversely, by using agents that disrupt growth factor protein complexes formed in vivo, growth factor-driven cell proliferation and/or migration may be suppressed such as for the purposes of treating cancers, psoriasis, atherosclerosis and wounds prone to hypertrophic scarring.

Description

field of invention [0001] The present invention relates to an isolated protein complex comprising a growth factor binding protein and vitronectin. In particular, the invention relates to an isolated protein complex comprising an insulin-like growth factor, insulin-like growth factor binding protein and vitronectin. The present invention also provides growth factor complexes comprising different growth factors and / or growth factor binding proteins that promote or enhance the formation of growth factor complexes. The present invention also provides methods of modulating cell proliferation and / or migration for wound repair, skin repair, cosmetic skin care and tissue repair treatments. Conversely, by disrupting protein complex formation in vivo, growth factor-driven cell proliferation and / or migration can be inhibited, eg, in the treatment of cancer, psoriasis, arteriosclerosis and wounds prone to scar overgrowth. These treatments may have medical and veterinary applications. ...

Claims

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Application Information

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IPC IPC(8): A61K38/00A61K38/30A61L27/00A61P1/00A61P1/04A61P5/00A61P9/10A61P17/02A61P17/06C12N15/09A61P19/00A61P19/04A61P19/10A61P25/00A61P35/00A61P37/00A61P43/00C07K14/47C07K14/475C07K14/485C07K14/50C07K14/51C07K14/71C07K14/75C07K14/78C07K14/79C07K19/00C12N5/10
CPCA61K38/30C07K14/71A61K47/48246C07K14/78A61K38/1709A61K38/39A61P1/00A61P1/04A61P17/00A61P17/02A61P17/06A61P19/00A61P19/04A61P19/08A61P19/10A61P25/00A61P35/00A61P35/04A61P37/00A61P43/00A61P5/00A61P9/10A61K2300/00C07K19/00
Inventor 齐·厄普顿珍妮弗·安·克里克尔
Owner FACTOR THERAPEUTICS LTD
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