EA009332B1 - Method of correction of immune state in aids' suffering patients - Google Patents

Abstract

The method relates to medicine, in particular, to endocrinology and immumology and provides correction of ACID pathologic immune process. The effectiviness of the method and exclusion of unfavorable effect on uninfected cells is enhanced by using an anti diotypic antibody to α-fetoprotein as a medicament in the method of correction organism's immune state, the method comprising administering said medicament.

Description

The invention relates to medicine, in particular to endocrinology and immunology, and concerns the correction of the pathological immune process in the syndrome of acquired immunodeficiency (AIDS).

There is a method of treating AIDS, consisting of cleaning the patient's blood from various viruses, including the retrovirus - the causative agent of AIDS (HIV), contaminated blood cells and microorganisms - associates using plasma sorption using an immunosorbent that is individually manufactured for each patient and is covalently amplified with it is a glucoprotein, which is isolated from human planceta and which exhibits an increased affinity for the AIDS retrovirus. The blood purification procedure involves the use of plasmapheresis directly following plasma adsorption with plasma replacement with an equal volume (1000-1200 ml) of the plasma substitute in the form of reopolyglucine and with repeated use of the plasma sorption using fresh immunosorbent. The blood purification course procedures are interspersed with the course application of specific immunostimulation using autovaccine prepared in each case on the basis of UV inactivated hemoculture from this patient (RF Patent No. 2105310, Cl. Ο01/33/54, 1998).

The disadvantage of this method is the complexity of the implementation.

There is a method of activation of the immune system, including the irradiation of x-rays, γ-rays, α-, β-particles, neutrons by sequential irradiation of an adult patient with doses of 3 szv (3 centiSiver or 3 Bzr), 6 szv, 15 szv, and in some cases 25 sSv, in especially critical cases 50 cSv, and the time before irradiation with a subsequent high dose should be sufficient to determine the appropriateness of such radiation by the doctor, the threshold values of the doses are selected taking into account the individual radiosensitivity of the patient and a wide range oxazolidinone sensitivity to radiation of various biological systems of human body (RF application number 94008814, cl. Α61Ν 5/10, 1997).

The use of X-ray and γ-radiation, α-, β-particles or neutrons complicates the method, which is thus unsafe, as it can cause radiation sickness.

There is a method of correcting the immune state of the body in acquired immunodeficiency syndrome, which includes administering to a person a therapeutically effective dose of an immunotoxin selected from the group of antiviral proteins chemically conjugated with a monoclonal antibody against reverse transcriptase of the HIV virus. Said antiviral proteins are selected from the group consisting of American phytolacca antiviral protein, gelonin, ricin, abrin, modecine, dodecandrin, saponin, volkensin and vicumin. The immunotoxin is chemically conjugated using cross-linking compounds selected from the group comprising the ester (RF Patent No. 2191596, cl. А61К 39/00, 2002).

The disadvantage of this method is the toxicity of the drug used and its insufficiently high efficiency, because after 24 hours of incubation, the immunotoxin, a monoclonal antibody to reverse transcriptase, the antiviral protein from phytolacca, killed about 65% of HIV-infected cells and 15% of uninfected, after 48 hours of incubation, killed about 95% of HIV-infected cells and 20% of uninfected.

The objective of the invention is to develop a method of correction of the immune state of the body, allowing you to eliminate violations of the immune status of the body caused by the human immunodeficiency virus.

Improving the efficiency of the method and the exclusion of adverse effects on uninfected cells is achieved by the fact that anti-idiotypic antibodies to α-fetoprotein are used as a medicine in the method of correcting the immune system of the body in AIDS patients, including the administration of a drug according to the invention.

The use of anti-idiotypic antibodies to α-fetoprotein increases the efficiency of the method and eliminates the toxic effect on uninfected cells with acquired immunodeficiency syndrome (AIDS).

To correct the immune state of the body, such an amount of anti-idiotypic antibodies to α-fetoprotein is injected in order to suppress the production of antibodies to them. Therefore, for each particular case, a therapeutically effective dose of the drug is determined experimentally.

A product is obtained from blood serum, lymph, hemolymph of human and female animals during pregnancy and after delivery in the lactation stage, as well as from eggs of animals and birds, fish eggs. An agent can be obtained from blood serum, milk, colostrum and other physiological body fluids of a donor after immunization with antibodies against α-fetoprotein or their PAB fragments.

For the preparation of a medicament, for example, goat milk serum is taken, obtained after curdling the milk and removing casein. The serum is centrifuged to separate from the residues of casein and saturated with ammonium sulfate, dissolving the dry salt in the serum to 20% saturation. The precipitate formed is removed by centrifugation. The supernatant is added to 35% saturation with ammonium sulfate, the resulting immunoglobulin precipitate is separated by centrifugation, dissolved in 0.9% sodium chloride solution and separated from ammonium sulfate by gel filtration on a Sephadex 0-50 column, equilibrated with 0.9% sodium chloride solution.

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The presence of anti-idiotypic antibodies to α-fetoprotein in the resulting drug is proved by ELISA using a sum of conventional or individual monoclonal antibodies specific to α-fetoprotein.

Anti-idiotypic antibodies to α-fetoprotein are applied as follows.

Example 1. Patient B., 20 years old, registered as HIV-infected since 2000. The cause of infection is intravenous drug administration. Diagnosed with HIV infection in stage 2B (generalized lymphadenopathy). The viral load was 10,000 copies in 1 ml of blood. Analysis of the activity of anti-idiotypic antibodies to α-fetoprotein against T-killer cells was performed on a patient’s blood cell culture. It was established that incubation of the blood cells of AIDS patients with a mixture containing an equal amount of anti-idiotypic antibodies to α-fetoprotein and complement, leads to complete selective destruction of T-killer cells in the blood.

Example 2. Anti-idiotypic antibodies to α-fetoprotein in the mixture with complement were added to the culture of uninfected cells and, accordingly, to the culture of chronically infected cells. When treating cells infected with a strain of HIV (H1U-AC-1) for 24 hours, complete destruction of infected cells occurred. At the same time, uninfected cells were not destroyed.

This confirms the selectivity of the drug.

Example 3. Patient W., 42, the diagnosis of melanoma, which developed as a result of infection of a patient with AIDS. Before treatment, he had the following hematological blood parameters: hemoglobin 97.0; erythrocytes 3.29; color index 0.88; leukocytes 21.6; ESR 65; T-helpers 0.619; T-suppressors 0,423; immune status of T-help. / T-supr. 1.46.

After the course of treatment with the proposed remedy, which was administered for 7 days in an amount of 20 mg per day, the following hematological blood parameters were obtained: hemoglobin 114.0; red blood cells 3.88; color index 0.88; leukocytes 11,4; ESR 5.0; T-helpers 1,958; T-suppressors 0,932; immune status of T-help. / T-supr. 2.1.

Example 4. Patient B., 51, the diagnosis of AIDS, which is accompanied by leukemia. Before treatment, blood counts were as follows: hemoglobin 37.0; red blood cells 1,29; color index 0.86; leukocytes 2.25; ESR 75.0; T-helper 3.1; T-suppressors 2.75; immune status of T-help. / T-supr. 1.13.

After a course of treatment for 10 days with the proposed remedy with immunoglobulins containing anti-idiotypic antibodies to α-fetoprotein, which was administered in an amount of 10 mg per day, the blood parameters changed as follows: hemoglobin 61.0; red blood cells 1.69; color indicator 1.0; leukocytes 1,9; ESR 40.0; T-helper 2.2; T-suppressors 1.9; immune status of T-help. / T-supr. 1.16

The advantage of this method is the absence of a negative effect of the used drug on the human or animal body.

Claims (1)

CLAIM A method for correcting the immune state of an organism in AIDS patients, comprising administering a drug, characterized in that antiidiotypic antibodies to α-fetoprotein are used as a drug.