WO1996039187A1 - Procede de traitement de molluscum contagiosum suite a une infection par vih - Google Patents

Procede de traitement de molluscum contagiosum suite a une infection par vih Download PDF

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Publication number
WO1996039187A1
WO1996039187A1 PCT/US1996/009192 US9609192W WO9639187A1 WO 1996039187 A1 WO1996039187 A1 WO 1996039187A1 US 9609192 W US9609192 W US 9609192W WO 9639187 A1 WO9639187 A1 WO 9639187A1
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WO
WIPO (PCT)
Prior art keywords
hiv
cells
patient
monoclonal antibodies
disease
Prior art date
Application number
PCT/US1996/009192
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English (en)
Inventor
D. Allen Allen
Original Assignee
Allen D Allen
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Allen D Allen filed Critical Allen D Allen
Priority to AU62567/96A priority Critical patent/AU6256796A/en
Priority to EP96921318A priority patent/EP0831907A4/fr
Publication of WO1996039187A1 publication Critical patent/WO1996039187A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2821—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against ICAM molecules, e.g. CD50, CD54, CD102
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2839—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily
    • C07K16/2845—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily against integrin beta2-subunit-containing molecules, e.g. CD11, CD18
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention relates generally to methods for treating
  • HIV immunodeficiency virus
  • T-lymphocytes or their lytics in order to inhibit or treat HIV and related
  • the present invention also includes a method of
  • HIV immunodeficiency virus
  • HIV human immunodeficiency virus
  • CTL cytotoxic T-lymphocytes
  • CD3 and CD4 antigens CD4+ T-lymphocytes
  • HIV immunodeficiency virus
  • CD4 + cells the number of cells infected is inadequate to account for
  • CTL's are beneficial for those infected with HIV since it is believed
  • CTL's help control the infection, i.e., CTL's are believed to be
  • lymphocyte population that includes CTL's.
  • HIV-infected humans have an anti-self, anti-CD4 CTL in
  • HIV-infected chimpanzees This is significant because HIV infection
  • T cell-monocyte adhesion pathways are important in HIV
  • CD18-ICAM-1 results in greater than 90% inhibition of HIV-1
  • lymphocytes CTL and their target cells.
  • CTL lymphocytes
  • HIV-infected chimpanzees have circulating CTL that lyse uninfected
  • CD4+ T cells Because HIV-infected chimpanzees do not develop HIV
  • HIV vaccine studies have shown that reducing CTL's causes the
  • the present invention is based on the deduction that the reason CD4 counts go down in the first place as a
  • T-lymphocyte is overcome according to the teachings of the present
  • S6F1 mouse antibodies utilizes monoclonal S6F1 mouse antibodies (S6F1 mAb) directed
  • CD4+ T lymphocytes from the peripheral blood of some adults with
  • RNA persisted thereby indicating that the newly circulating cells are
  • THF thymic humoral factor
  • Another primary objective is to neutralize HIV-producing
  • FIGURE 1 is a schematic representation of AIDS pathogenesis
  • FIGURE 2 is a schematic representation of a S6F1 monoclonal
  • FIGURE 3 illustrates the placement of antigen and control on a
  • FIGURE 4 shows mean T cell/mm 3 v. weeks since infusion of
  • FIGURES 5(a)-(d) show the results of several patients treated in
  • FIGURE 6 shows the results of a patient with advanced HIV
  • FIGURE 7 compares the results of treatment of S6F1 mAb
  • FIGURE 8 illustrates response to second infusion in accordance
  • FIGURE 9 shows the arithmetic mean of CD8% and CTL% of T
  • TTL's T-lymphocytes
  • CTL kills foreign cells (such as bacteria, fungus, viruses, cancer or the
  • CTL's belong to a group of lymphocytes that carry a CD8
  • HIV vaccine studies have shown that reducing CTL's causes
  • S6F1 mouse antibodies (S6F1 mAb) are directed against an epitope of LFA-1 .
  • S6F1 mAb is directed against an epitope of LFA-1 .
  • lymphocytes as contrasted with suppressor CD8 + T cells.
  • present invention is not limited to the use of mouse antibodies.
  • LFA-1 LFA-1
  • ICAM monoclonal antibodies are also directed against the
  • FIGURE 1 is a schematic representation of what is believed to
  • these cells carry various known antigens
  • DR including, without limitation, DR, CD8, LFA-1 , ICAM and TCR-1 .
  • cells also include one or more lytics which are chemical compounds
  • lytics used to attack the target cell; such lytics also include antigens.
  • the present invention overcomes the destructive action of the
  • monoclonal antibody is an antibody that is made from one cell so that
  • FIGURE 2 a representation is shown of the
  • anti-self, anti-CD4 CTL are produced in the conventional manner and
  • the present invention is intended to cover all such elements
  • monoclonal antibodies are infused.
  • the daily regimen is preferably
  • an effective immune response will typically mean that the
  • the patient's skin has an improved delayed cutaneous hypersensitivity
  • monoclonal antibodies are typically supported in a suitable carrier such as
  • the infusion may be effected using a conventional syringe
  • the present invention is that it provides a method of neutralizing the
  • the HIV disease can be transformed
  • S6F1 refers to a mouse antibody directed against an epitope of
  • LAF-1 and ICAM refer to monoclonal
  • HIV could be cultured from his blood cells
  • the patient was given about 68
  • the AIDS virus could no longer be
  • the dosage range varies from about 0.01 to about 1 .0
  • PCP pneumocystis carinii pneumonia
  • S6F1 LDB1 1 LDH10 One suitable S6F1 clone, S6F1 LDB1 1 LDH10, is disclosed in
  • T cell phenotypes were enumerated by a 3-color flow cytometry
  • Becton-Dickinson are suitable for use in accordance with the method
  • HIV RNA was measured by polymerase chain reaction (PCR) in
  • RNA guanidine/plant chloroform. The purified RNA was divided into two
  • Negative controls were of two types: blanks with
  • the response to an antigen is positive if, and only
  • lymphocyte counts or functions are lymphocyte counts or functions.
  • Each patient was infused with about 7 mg (approximately 0.1
  • FIGURES 5(a)-(c) show the results for three patients with early
  • FIGURE 5(d) illustrates the
  • HIV RNA will necessarily increase when a patient is
  • FIGURE 6 illustrates the results for a patient with more
  • Thymic humoral factor has been reported to increase CD4 count and improve
  • FIGURE 7 shows the results of a patient who had no detectable
  • CD3 + CD4-CD8- T lymphocytes may offer little protection against
  • This patient had a 2-log increase in HIV RNA
  • HAMA human anti-mouse antibodies
  • the patient was reinfused using a single dose of 7 mg as described in
  • Example 2 At the time of reinfusion, the patient had a marked CD4 +
  • FIGURE 6 did not exhibit replacement of double-marked T cells when
  • FIGURE 7 Within two weeks of being reinfused, the patient being
  • HAMA may also avoided by removing the heavy chains in
  • human antibodies are suitable for use in accordance with the
  • FIGURE 6 suggest that the CD8 + T cell significance is not yet
  • lymphocytes at all for greater than three months and there were no
  • HIV RNA The latter may have been due to an unrelated HIV vaccine
  • the patient received two weeks into treatment in accordance with the
  • an infusion of HIV virions may be any infusion of HIV virions.
  • CD4 count It is well known that CD4 cell function, and not simply
  • CD4 count plays an important role in immunocompetence.
  • a flow cytometer will count any lymphocyte that bears the CD3
  • T cell and CD4 markers as a CD4+ T lymphocyte. This includes
  • the patient also had 900 CD8 cells and a total of 900 T cells, meaning
  • CD4 + CD8 + thymocytes express only a few CD4 + CD8 + thymocytes.
  • TCR T cell receptors
  • HIV disease has been the subject of considerable debate and
  • Lymphocytes is Increased During HIV-lnfection", Clin Exp Immunol..
  • TcRgd + lymphocytes were found to be increased in the
  • the patient whose results are shown in FIGURE 5(c) may have
  • the present invention establishes that there are two distinct
  • immunodeficiency may be reversible if the HIV-producing cells are
  • Anti-adhesion antibodies can be used to neutralize HIV-producing cells
  • ICAM-2 AND ICAM-3 monoclonal antibodies on CD4 + T lymphocyte
  • ICAM-1 ICAM-1
  • ICAM-2 ICAM-3
  • Butini article included the hybridoma cell lines for TS1 /22 and
  • CD4 + T cells remain completely viable until day ten after infection and showed only a minor depletion of CD4 + T cells
  • HIV human immunodeficiency virus
  • Molluscum contagiosum is a skin disease that is known to
  • HIV human immunodeficiency virus
  • the lesions caused by the disease may be excised
  • the patient was a 45 year old male with advanced AIDS.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne des méthodes de traitement et d'inhibition de la maladie et des symptomes associés au virus d'immunodéficience humaine (VIH). Le procédé consiste à transformer une infection par le virus d'immunodéficience humaine (VIH) en une maladie non grave en ayant recourt à l'infusion d'anticorps monoclonaux dirigés contre des antigènes particuliers sur des T-lymphocytes cytotoxiques anti-soi, anti-CD4. Le procédé est également utile pour traiter molluscum contagiosum dû à une infection par le virus d'immunodéficience humaine (VIH).
PCT/US1996/009192 1995-06-06 1996-06-06 Procede de traitement de molluscum contagiosum suite a une infection par vih WO1996039187A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU62567/96A AU6256796A (en) 1995-06-06 1996-06-06 Method for treating molluscum contagiosum resulting from hiv infection
EP96921318A EP0831907A4 (fr) 1995-06-06 1996-06-06 Procede de traitement de molluscum contagiosum suite a une infection par vih

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US46735695A 1995-06-06 1995-06-06
US08/467,356 1995-06-06

Publications (1)

Publication Number Publication Date
WO1996039187A1 true WO1996039187A1 (fr) 1996-12-12

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/009192 WO1996039187A1 (fr) 1995-06-06 1996-06-06 Procede de traitement de molluscum contagiosum suite a une infection par vih

Country Status (3)

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EP (1) EP0831907A4 (fr)
AU (1) AU6256796A (fr)
WO (1) WO1996039187A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990013281A2 (fr) * 1989-04-28 1990-11-15 Baylor College Of Medicine Procede de suppression d'une infection par l'hiv
US5002869A (en) * 1987-11-02 1991-03-26 Dana-Farber Cancer Institute Monoclonal antibody specific to a novel epitope of the LFA-1 antigen of human T lymphocytes

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU5553290A (en) * 1989-04-28 1990-11-29 Baylor College Of Medicine Dissemination of hiv-1 infected cells
JPH08500826A (ja) * 1992-08-21 1996-01-30 ジェネンテク，インコーポレイテッド Ｌｆａ−１仲介疾患を処置する方法
AU684074B2 (en) * 1993-03-19 1997-12-04 Allen D. Allen Methods for inhibiting HIV associated disease using monoclonal antibodies directed against anti-self cytotoxic T-cells
WO1995028176A1 (fr) * 1994-04-15 1995-10-26 Allen Allen D Procede de traitement de l'infection a vih par anticorps actifs contre les lymphocytes t cytotoxiques et par le facteur humoral thymique

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5002869A (en) * 1987-11-02 1991-03-26 Dana-Farber Cancer Institute Monoclonal antibody specific to a novel epitope of the LFA-1 antigen of human T lymphocytes
WO1990013281A2 (fr) * 1989-04-28 1990-11-15 Baylor College Of Medicine Procede de suppression d'une infection par l'hiv

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
ARCH. VIROL., 1995, Vol. 140, SCHEGLOVITOVA et al., "Antibody to ICAM-1 Mediates Enhancement of HIV-1 Infection of Human Endothelial Cells", pages 951-958. *
CELLULAR IMMUNOLOGY, 1994, Vol. 156, DEZZUTTI et al., "Modulation of HTLV-II-Associated Spontaneous Lymphocyte Proliferation by Beta 2 Integrin CD11a/CD18 Involves Interaction with its Cognate Ligand, CD54", pages 113-123. *
J. EXP. MED., April 1989, Vol. 169, TSUBOTA et al., "A Cytotoxic T Lymphocyte Inhibits Acquired Immunodeficiency Syndrome Virus Replication in Pirepheral Blood Lymphocytes", pages 1421-1434. *
J. EXP. MED., February 1994, Vol. 179, DE FOUGEROLLES et al., "Characterization of the Function of Intercellular Adhesion Molecule (ICAM)-3 and Comparison with ICAM-1 and ICAM-2 in Immune Responses", pages 619-629. *
See also references of EP0831907A4 *

Also Published As

Publication number Publication date
AU6256796A (en) 1996-12-24
EP0831907A1 (fr) 1998-04-01
EP0831907A4 (fr) 2005-05-04

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