Use of parvovirus capsid particles in the inhibition of cell proliferation and migration

Inactive Publication Date: 2006-06-29
BROLIDEN KRISTINA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009] It has been discovered that the B19 parvovirus capsid, B19 parvovirus capsid proteins, or fragments thereof inhibit the growth and / or migration of cells that have a receptor that interacts with a parvovirus B19 capsid or fragment thereof (e.g., a P antigen containing cell). The data presented herein demonstrate that the B19 parvovirus capsid, B19 parvovirus capsid proteins, and fragments thereof, inhibit hematopoiesis and endothelial cell growth and migration. Accordingly, the compositions described herein can be used to reduce the production of red blood cells, white blood cells, and blood platelets, as well as, inhibit the growth and migration of other cells having a receptor that interacts with a parvovirus B19 capsid or fragment thereof (e.g., a P antigen containing cell), such as endothelial cells. Because many diseases or maladies are associated with an overproduction of cells of hematopoietic origin and / or invasive growth or migration of cells of endothelial origin, the compositions and methods described herein have significant therapeutic and prophylactic utility.

Problems solved by technology

While many are trying to prevent B19 parvovirus infection by administering B19 parvovirus capsids, none have sought to exploit the properties of the B19 parvovirus capsid, B19 parvovirus capsid proteins, or fragments thereof to develop novel medicaments that inhibit cell proliferation or migration.

Method used

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  • Use of parvovirus capsid particles in the inhibition of cell proliferation and migration
  • Use of parvovirus capsid particles in the inhibition of cell proliferation and migration
  • Use of parvovirus capsid particles in the inhibition of cell proliferation and migration

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Embodiment Construction

[0038] It has been discovered that the B19 parvovirus capsid, B19 parvovirus capsid proteins, or fragments thereof inhibit the growth and / or migration of cells that have a receptor that interacts with a parvovirus B19 capsid or fragment thereof (e.g., a P antigen containing cell). By using colony formation assays, it was determined that B19 parvovirus capsids composed of VP1 and VP2 or VP2 alone inhibit hematopoiesis and, thus, the growth of several different types of cells of hematopoietic origin including human fetal liver cells, human umbilical cord blood cells, and adult bone marrow cells. Using the same type of colony formation assay, it was discovered that B19 parvovirus capsids inhibit the growth of bone marrow cells obtained from Baboons and Macaques. Further, using colony formation assays, it was discovered that fragments of VP2, whether prepared by enzymatic digestion of intact VP2 capsids or by synthesis of peptides corresponding to various regions of VP2, inhibit hematop...

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Abstract

The invention described herein relates to the discovery of methods and compositions for the inhibition of growth and / or migration of cells that have a receptor that interacts with a parvovirus B19 capsid or fragment thereof (e.g., a P antigen containing cell), including but not limited to, cells of hematopoietic origin and endothelial cells. More specifically, parvovirus capsid particles or fragments of parvovirus capsid proteins are used to manufacture medicaments that can be administered to a subject to inhibit hematopoietic progenitor cell growth (e.g., prior to stem cell transplantation), endothelial cell growth, (e.g., as an anti-tumorigenesis treatment or to prevent restenosis or fibrotic build up following prosthetic implantation), or to prevent disorders that involve the abnormal proliferation of cells that have the P antigen (e.g., Polycythemia Vera).

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. application Ser. No. 09 / 991,433, filed on Nov. 16, 2001, which is a continuation-in-part of U.S. application Ser. No. 09 / 447,693, filed Nov. 23, 1999, now abandoned, which claims priority to Swedish Patent Application No. 9804022-3, filed Nov. 24, 1998. This application is also a continuation in part of U.S. application Ser. No. 10 / 200,616, filed Jul. 19, 2002, which is a continuation of U.S. application Ser. No. 09 / 447,693, filed Nov. 23, 1999, now abandoned, which claims priority to Swedish Patent Application No. 9804022-3, filed Nov. 24, 1998. [0002] This application claims priority to U.S. application Ser. No. 10 / 200,616, U.S. application Ser. No. 09 / 991,433, U.S. application Ser. No. 09 / 447,693, and Swedish Patent Application No. 9804022-3, all of which are hereby expressly incorporated by reference in their entireties.FIELD OF THE INVENTION [0003] The present invention relates to the disc...

Claims

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Application Information

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IPC IPC(8): A61K38/00C12Q1/68A01N37/18A61K38/16
CPCA61K38/162C07K14/005C12N2750/14322C12N2750/14323C12N2750/14333
Inventor BROLIDEN, KRISTINAWESTGREN, MAGNUS
Owner BROLIDEN KRISTINA
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