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Antibodies directed against cellular coreceptors for human immunodeficiency virus and methods of using the same

a technology antibodies, which is applied in the field of infection by and pathogenesis of human immunodeficiency virus, can solve the problems of rapid development of viral strains, inability to infect cells, and inability to infect macrophage tropic strain ba-l

Inactive Publication Date: 2006-04-04
THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0019]The invention also relates to a method of inhibiting infection of a cell by HIV comprising adding to the cell an anti-immunodeficiency virus antibody capable of binding to a cellular protein on the cell, wherein upon binding of the antibody to the cellular protein infection of the cell by HIV is inhibited.
[0020]Also included in the i

Problems solved by technology

However, the macrophage tropic strain Ba-L, is not capable of infecting cells which co-express both CXCR4 and CD4.
While these therapies, particularly when used in combination with one another, are effective, they are frequently short-lived in that viral strains rapidly develop that are resistant to one or more of the compounds used.

Method used

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  • Antibodies directed against cellular coreceptors for human immunodeficiency virus and methods of using the same
  • Antibodies directed against cellular coreceptors for human immunodeficiency virus and methods of using the same
  • Antibodies directed against cellular coreceptors for human immunodeficiency virus and methods of using the same

Examples

Experimental program
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Effect test

example 1

Inhibition of HIV by a Monoclonal Antibody to a Coreceptor (CXCR4) is both Cell Type and Virus Strain Dependent

[0098]The data presented herein establish that 12G5 is a mouse MAb that specifically recognizes CXCR4 but not other members of the chemokine receptor family, including CCR1-5 and CXCR1 and CXCR2 (interleukin-8 receptors α and β, respectively).

[0099]In FIG. 1A there is shown the levels of cell surface CXCR4 expression determined by flow cytometry following 12G5 staining of the CD4+ T-cell lines MOLT-4 and C8166, the CD4-transfected human rhabdomyosarcoma cell line RD, and the human glioma cell line U87 as well as primary macrophages purified by adherence to plastic and cultured for 1 or 5 days (McKnight et al., 1995, J. Virol. 69:3167-3170; and Simmons et al., 1995, Virology 209:696-700). Flow cytometry was carried out as previously described (McKnight et al., 1996, J. Virol. 70:4598-4606).

[0100]HIV infectivity of macrophages or PBMCs is routinely estimated by infecting cell...

example 2

CD4-Independent Infection by HIV-2 is Mediated by Fusin / CXCR4

[0115]The Experimental Procedures used in Example 2 are now described. Cells CD4-positive human T lymphoid cell lines, Sup-T1, Hut-78, H9, CEM, Molt4-clone8, and the TxB cell hybrid line, CEMx174, have been described previously (Hoxie et al., 1986, Science 234:1123-1127; Hoxie et al., 1988, J. Virol. 62:2557-2568; LaBranche et al., 1994, J. Virol. 68:5509-5522). CD4-negative T lymphoid lines HSB and CEMss4− are described (Weiner et al., 1991, Pathobiol. 59:361-371 and Nara et al., 1987, AIDS Res. and Hum. Retroviruses 3:283-202, respectively) and BC7 was derived from Sup-T1 cells, as described in Table 4. Human B cell lines, Nalm6, KM3.79, and REH are described (McKnight et al., 1995, J. Virol. 69:3167-3170; McKnight et al., 1996, J. Virol. 70:4598-4606) Hela, RD, and Daudi cells have been described previously (Clapham et al., 1991, supra 5; Clapham et al., 1992, supra). 293T and CCCS-L-cells are well known in the art and ...

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PUM

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Abstract

The invention relates to an anti-immunodeficiency virus antibody which binds to a cellular protein and diagnostic and therapuetic methods of using the same.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority under 35 U.S.C. §119(e) (1) to U.S. Provisional Application Ser. Nos. 60 / 020,396 and 60 / 020,647, filed on Jun. 25 and Jun. 27, 1996, respectively.GOVERNMENT SUPPORT[0002]The invention was supported in part by a grant from the U.S. Government (NIH Grant No. AI 33854) and the U.S. Government may therefore have certain rights in the invention.FIELD OF THE INVENTION[0003]The field of the invention is infection by and pathogenesis of Human Immunodeficiency Virus.BACKGROUND OF THE INVENTION[0004]The human immunodeficiency viruses HIV-1 and HIV-2 and the closely related simian immunodeficiency viruses (SIV), all use the CD4 molecule as a receptor during infection. Other cellular molecules have long been suspected to form an essential component of the cellular HIV receptor; however, the nature of such cellular molecules was not known until the discovery of fusin (Feng et al., 1996, Science 272:872-876; Maddon et a...

Claims

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Application Information

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IPC IPC(8): C07K16/28A61K38/00
CPCA61K38/00C07K16/2866
Inventor HOXIE, JAMES A.
Owner THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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