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Anti-idiotypic antibody and its use in diagnosis and therapy in HIV-related disease

a technology of anti-idiotypic antibodies and hiv-related diseases, which is applied in the field of diagnosis and treatment of aids, can solve the problems of destroying the immune system, the true impact of the disease has yet to be felt, and the personal, social and economic impact of aids will be enormous, so as to influence the anti-idiotypic regulation of t cells and regulate the immune respons

Inactive Publication Date: 2005-10-06
RAPID MEDICAL DIAGNOSTICS CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides compounds that can target a common idiotope found in multiple types of human anti-HIV-1 antibodies. One of these compounds, designated 1F7, is specifically reactive with at least three human anti-HIV-1 antibodies and non-reactive with human non-HIV antibodies. The idiotope recognized by 1F7 is involved in the clonal suppression of B cells characteristic of HIV infection and also affects T cell anti-idiotypic regulation. The invention provides a method of regulating the immune response in HIV-infected individuals by treatment with the anti-idiotypic antibody. The presence of the idiotope in the sera of HIV-infected individuals is also found to correlate with HIV-related pathologies, such as HIV-related B cell lymphoma. The invention provides a method of diagnosing and monitoring HIV-related pathologies by the reaction of the HIV-infected sera with the anti-idiotypic antibody.

Problems solved by technology

However, the true impact of the disease has yet to be felt.
Thus, if unchecked, the personal, social and economic impact of AIDS will be enormous.
However, despite the presence of cellular and humoral immunity in the infected individual, the virus persists and after several years of latency will become active, often mutating to variant forms, and eventually destroying the immune system leading to full-blown AIDS.
Individuals who test positive for HIV-1, however, are unable to clear the infection through these two types of immune response.
However, this explanation is difficult to defend since the T4 count remains normal and only a small fraction of T4 cells appears to be infected during the long latent and asymptomatic phases of the disease.
However, there are drawbacks to these traditional methods.
Subjects entering the symptomatic stages of disease often fail to recognize the onset of symptoms and delay seeking help.
Currently there is no effective treatment for HIV-infection.
No effective vaccine is presently available.
AZT and other pharmaceutical compounds can temporarily alleviate symptoms in AIDS patients, but have been unable to stimulate the immune system to clear the virus.

Method used

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  • Anti-idiotypic antibody and its use in diagnosis and therapy in HIV-related disease
  • Anti-idiotypic antibody and its use in diagnosis and therapy in HIV-related disease
  • Anti-idiotypic antibody and its use in diagnosis and therapy in HIV-related disease

Examples

Experimental program
Comparison scheme
Effect test

example i

Isolation and Characterization of Anti-Idiotypic Antibody

1. Materials

[0064] Human polyclonal anti-HIV immunoglobulin (HIVIG), lot VH 102 was obtained from NIAID AIDS Research reference Reagent Program (ERC Bioservices Corporation, Rockville, Md.). Human pooled IgG (IVIG) was purchased from Cutter Biological, Elkhart, Ind. Normal human HIV-sera was obtained from the San Diego Regional Blood Bank. HIV positive (HIV+) sera from healthy, seropositive individuals were obtained from North American Biological Inc. (NABI), Miami, Fla.

[0065] Recombinant p24. (HTLV-IIIB) and the p24 / gp41 fusion protein were obtained from Dr. Torsten Helting, Pharmacia Genetic Engineering, La Jolla, Calif. Recombinant gp120 (HTLV IIIB), or gp120 (MN) V3 loop peptides, and recombinant HIV-1 reverse transcriptase (RT, p65) were purchased from American Biotechnologies, Inc., Cambridge, Mass. Recombinant gp120 (SF2) was obtained from Chiron Corporation, Emeryville, Calif. The antigen designations IIIB, MN, SF2,...

example ii

Clonotypic Analysis of HIV+ and HIV− Human Serum

[0086] According to the Western blot show in FIG. 1 described above, three 1F7 reactivity patterns with HIV+ sera were observed. In one group, represented by #14 HIV+ serum, 1F7 reacted to antibodies to more than one HIV antigen. In the second group, represented by #3 HIV+ serum, 1F7 showed reactivity only with anti-core (p24) antibodies. Serum from the third group showed no 1F7-positive anti-HIV antibodies.

[0087] Further testing was performed in order to analyze the representation of these three groups in HIV+ sera. The detection of anti-gp120and anti-p24 antibodies, and in addition, the detection of 1F7 Id+ on antibodies against gp120and p24 in HIV+ sera was determined as follows. First, anti-HIV antibodies were detected as described above, by coating microtiter plates with 200 ng / well of gp120 or p24. A 1:40 dilution of HIV+ individual serum was added and incubated. The antibodies which bound to gp120 and p24 were determined by pe...

example iii

Evidence that Anti-HIV Antibody Responses in HIV+ Individuals are of Restricted Clonal Origin

A. Determining Clonal Restriction of B-Cell Clones by Kappa / Lambda Light Chain Analysis

1. Methods

[0092] Purification of human serum antibodies was performed by coupling recombinant p24 (HIV-1 IIIB) (Pharmacia Genetic Engineering, La Jolla, Calif.) and recombinant gp120(SF-2) (Chiron Corporation, Emeryville, Calif.) to CNBr-activated Sepharose 4B (Pharmacia LKB, Biotechnology AB, Uppsala, Sweden). According to the manufacturer, IgG from HIV+ sera (North American Biological, Inc., Miami, Fla.) was purified on protein G sepharose. The Ig fraction was passed over affinity columns at 5 ml / hour. After washing, the column was eluted using 0.1M glycine buffer (pH 2.5) with 0.01 M PBS (pH 7.0). The antibodies were dialyzed and concentrated for further use.

[0093] Detection of antibody light chain isotypes in normal (San Diego Regional Blood Bank, San Diego, Calif.) and unfractionated HIV+ human se...

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Abstract

The present invention provides an anti-idiotypic antibody having specific reactivity with an idiotope common to more than one type of anti-HIV-1 antibody, and having no specific reactivity with non-HIV-1 antibodies. The present invention provides methods of diagnosis, monitoring and treatment of HIV-related diseases through the use of this antibody or related compounds.

Description

RELATED APPLICATIONS [0001] This application is a continuation-in-part of application U.S. Ser. No. 07 / 848,327, filed Mar. 9, 1992, the contents of which are hereby incorporated by reference.ACKNOWLEDGEMENT [0002] This invention was made with the support of government grants RFA-N11-1-NIAID-87-CA-03 and R01CA51434-01 from the National Institute of Health. Therefore, the United States government may have rights in the invention.BACKGROUND OF THE INVENTION [0003] This invention relates to the diagnosis and treatment of AIDS and more specifically to an anti-idiotypic antibody reactive with more than one type of anti-HIV-1 antibody. The invention further relates to the use of the anti-idiotypic antibody as a diagnostic and therapeutic agent. [0004] Acquired Immune Deficiency Syndrome, or AIDS, has been described as a modern plague. In the decade since its first description in 1981, it has claimed 120,000 victims in the United States alone. Currently almost 200,000 people are known to be...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/00C07K16/10C07K16/42C12N5/06C12N5/20C12P21/08C12Q1/70
CPCA61K38/00A61K2039/505C07K16/1054C07K16/1063C07K16/4225C07K2317/21C07K2317/50C07K2317/73Y10S530/866Y10S435/974
Inventor MULLER, SYBILLEWANG, HAITAO
Owner RAPID MEDICAL DIAGNOSTICS CORP
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