Rg1 antibodies and application thereof

FIELD: pharmacology.

SUBSTANCE: present invention refers to immunology and biotechnology. There is offered recovered human antibody to RG1 polypeptide. There are described versions of antibodies, including one-chain antibody, and immunoconjugate based on said antibodies. There are disclosed methods of selective cell destruction, cell inhibition, treatment of disease state, detection of disease state, detection of RG1, monitoring of clinical course of prostate cancer, prediction in a person with using antibodies and immunoconjugate.

EFFECT: application of the invention provides new antibodies to RG1 polypeptide that can find application in treating tumours with RG1 overexpression.

16 cl, 4 dwg, 1 tbl, 13 ex

 

The text descriptions are given in facsimile form.

1. The selected human antibody or antigennegative fragment that contains a variable area light chain:
a) comprising the amino acid sequence shown in SEQ ID NO:26 or SEQ ID NO: 29, or
b) encoded by the nucleotide sequence shown in SEQ ID NO:20 or SEQ ID NO:23,
and moreover, the antibody or antigennegative fragment binds an RG1 polypeptide that has the amino acid sequence shown in SEQ ID NO:2.

2. The selected human antibody or antigennegative the first fragment, which contains variable plot heavy chain:
a) comprising the amino acid sequence shown in SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:30 or SEQ ID NO:31,
b) encoded by the nucleotide sequence shown in SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24 or SEQ ID NO:25, and the antibody or antigennegative fragment binds an RG1 polypeptide that has the amino acid sequence shown in SEQ ID NO:2.

3. The selected human antibody or antigennegative fragment, which contains:
a) variable area light chain having the amino acid sequence shown in SEQ ID NO:26, and variable plot heavy chain having the amino acid sequence of SEQ ID NO:27 or SEQ ID NO:28, or
b) variable area light chain having the amino acid sequence shown in SEQ ID NO:29, and variable plot heavy chain having the amino acid sequence of SEQ ID NO:30 or SEQ ID NO:31,
and moreover, the antibody or antigennegative fragment binds an RG1 polypeptide that has the amino acid sequence shown in SEQ ID NO:2.

4. The antibody according to claim 3, in which the flexible section of the heavy chain has the amino acid sequence shown in SEQ ID NO:27.

5. The antibody according to claim 3, in which the flexible section of the heavy chain has the amino acid sequence, which can be found in SEQ ID NO:28.

6. The antibody according to claim 3, in which the flexible section of the heavy chain has the amino acid sequence shown in SEQ ID NO:30.

7. The antibody according to claim 3, in which the flexible section of the heavy chain has the amino acid sequence shown in SEQ ID NO:31.

8. The selected human antibody or antigennegative fragment linking RG1 polypeptide that has the amino acid sequence shown in SEQ ID NO:2, and containing:
a) a CDR3 sequence of a light chain comprising amino acid residues 110-117 amino acid sequence shown in SEQ ID NO:26,
b) a CDR3 sequence of a heavy chain including amino acid residues 117-132 amino acid sequence shown in SEQ ID NO:27,
b) CDR1 CDR2 sequence and the sequence of the light chain comprising amino acid residues 44-55 amino acid sequence shown in SEQ ID NO:26, and 71-77 amino acid sequence shown in SEQ ID NO:26, respectively,
d) CDR1 CDR2 sequence and the sequence of the heavy chain including amino acid residues 50-54 amino acid sequence shown in SEQ ID NO:27, and 69-84 amino acid sequence shown in SEQ ID NO:27, respectively.

9. The selected human antibody or antigennegative fragment linking RG1 polypeptide, to the which has the amino acid sequence, shown in SEQ ID NO:2, and containing:
a) a CDR3 sequence of a light chain comprising amino acid residues 110-117 amino acid sequence shown in SEQ ID NO:29,
b) a CDR3 sequence of a heavy chain including amino acid residues 117-126 amino acid sequence shown in SEQ ID NO:30,
b) CDR1 CDR2 sequence and the sequence of the light chain comprising amino acid residues 44-55 amino acid sequence shown in SEQ ID NO:29, and 71-77 amino acid sequence shown in SEQ ID NO:29, respectively,
d) CDR1 CDR2 sequence and the sequence of the heavy chain including amino acid residues 50-54 amino acid sequence shown in SEQ ID NO: 30, and 69-84 amino acid sequence shown in SEQ ID NO:30, respectively.

10. The fragment of the antibody according to any one of claims 1, 2, 3, 8 or 9, where the antibody fragment is selected from the group of fragments, comprising an Fv, F(ab')-, F(ab')2-, scFv fragments, fragments of Minitel and dietel.

11. Immunoconjugate containing antibody or antibody fragment according to any one of claims 1, 2, 3, 8 or 9, in which the antibody or antibody fragment anywhereman with the molecule, which is a therapeutic agent or detectable marker.

12. Immunoconjugate according to claim 11, in which therapeutic agent is a cytotoxic among the STV.

13. Immunoconjugate indicated in paragraph 12, in which the cytotoxic agent selected from the group including ricin, doxorubicin, daunorubicin, paclitaxel, ethidiumbromid, mitomycin, etoposide, teniposide, vincristine, vinblastine, colchicine, dihydroxyanthracene, actinomycin D, diphtheria toxin, Pseudomonas endotoxin (D) AND, RE, ricin, abrin, glucocorticoid and radioactive isotopes.

14. Immunoconjugate indicated in paragraph 12, in which the cytotoxic agent is a radioactive isotope, which is chosen from the group including46Sc,47Sc,48Sc,72Ga73Ga90Y67Cu109Pd11Ag149Pm,153Sm166Ho,177Lu,186Re,188Re,211At,211Bi212Bi213Bi and214Bi.

15. Immunoconjugate according to claim 11, in which the detectable marker is a radioactive label, an enzyme, a chromophore or a fluorescent agent.

16. Immunoconjugate indicated in paragraph 15, in which the detectable marker is a radioactive isotope selected from the group including43Sc,44Sc,52Fe55Co.,68Ga64Cu86Y94mTc111In and99mTc.

17. Immunoconjugate according to claim 11, in which the conjugation of the antibody or fragment of antibody with a therapeutic agent or detectable marker is performed using chelate compound selected from the group comprising n-SN-benzyl-WRT and its derivatives, 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraoxo acid (DOTA) and its derivatives, and 1,4,7-triazacyclononane-N,N',N"-trioxane acid (NOTA) and its derivatives.

18. Immunoconjugate on 17, which is used to chelate compound represents cyclohexyl-DTPA (CNH-A"-DTPA) or MX-DTPA(1B4M-DTPA).

19. The antibody according to any one of claims 1, 2, 3, 8 or 9, where the antibody is a monoclonal antibody.

20. Single-stranded molecule antibodies that bind the RG1 polypeptide that has the amino acid sequence shown in SEQ ID NO:2, where the single-stranded molecule of the antibody includes antigennegative plot antibody according to claims 1, 2, 3, 8 or 9.

21. Polypeptide that binds RG1 polypeptide having the amino acid sequence shown in SEQ ID NO:2, where the specified polypeptide includes antigennegative plot antibody according to claims 1, 2, 3, 8 or 9.

22. The method of selective destruction of cells expressing the polypeptide RG1 person having the amino acid sequence represented in SEQ ID NO:2, which includes the interaction of a cell with an effective amount of immunoconjugate on any of 11, 12, 13, 14, 15, 16, 17 or 18, which selectively destroy the cell expresses the polypeptide RG1 person having the amino acid sequence represented in SEQ ID NO:2.

23. Method of inhibiting cell expressing the polypeptide R1 man, having the amino acid sequence represented in SEQ ID NO:2, which includes the interaction of the cells with an effective amount of the antibody according to any one of claims 1 to, 2, 3, 4, 5, 6, 7, 8, 9, 10, 19 or 20, where inhibiting cell expresses the polypeptide RG1 person having the amino acid sequence represented in SEQ ID NO:2.

24. A method for the treatment of painful conditions in humans associated with the expression of RG1 polypeptide having the amino acid sequence represented in SEQ ID NO:2, which provides for the introduction to the patient a therapeutically effective amount immunoconjugate on any of 11, 12, 14, 15, 16, 17 or 18, so is the treatment of the specified condition.

25. The way to identify a painful condition in the subject, which is associated with the expression of RG1 polypeptide having the amino acid sequence shown in SEQ ID NO:2, and the method includes:
(a) introduction to the subject immunoconjugate on any of 11, 12, 13, 14, 15, 16, 17 or 18;
(b) determining the binding immunoconjugate in the body of the subject and
(C) determining whether the binding immunoconjugate the subject has increased compared with the level of binding that is defined in the control subjects without the disease, and, thus, revealing a painful condition in the subject.

26. The way to detect the Oia presence of the RG1 polypeptide, having the amino acid sequence shown in SEQ ID NO:2 in a biological sample, which includes:
(a) obtaining a biological sample from the subject;
(b) contacting the biological sample with the antibody according to any one of claims 1 to, 2, 3, 4, 5, 6, 7, 8, 9, 10, 19 or 20, which specifically binds the RG1 polypeptide having the amino acid sequence shown in SEQ ID NO:2; and
(C) detection of binding of the monoclonal antibody or its fragment in a biological sample
and thus, the detection of the presence of the RG1 polypeptide having the amino acid sequence shown in SEQ ID NO:2 in a biological sample.

27. The method according to p, where the detecting includes:
(a) contacting the monoclonal antibody or its fragment, which are associated with the RG1 polypeptide, with the second antibody, labeled with detectable marker so that the formed complex, which complex comprises a monoclonal antibody or a fragment associated with the RG1 polypeptide, and the second antibody, and
(b) detection of the thus formed complex and the presence of the RG1 polypeptide having the amino acid sequence shown in SEQ ID NO:2 in a biological sample.

28. The way to identify a painful condition in the subject, which is associated with the expression of RG1 polypeptide having the amino acid sequence set is built in SEQ ID NO:2, providing for detection of the presence of the RG1 polypeptide by the method according to item 27, wherein an increased level of binding of the monoclonal antibody compared to the binding defined in the control subjects without the disease, indicates a painful condition in the subject.

29. The method of controlling the flow of prostate cancer in the subject, including quantification in the first biological sample of the subject the presence of the RG1 polypeptide having the amino acid sequence shown in SEQ ID NO:2, using the method according to item 27, and the comparison of a given thus amount to the amount that is present in a second biological sample of the subject, and these samples were taken at different times, and the difference in the designated number is a measure of the flow of prostate cancer.

30. The method according A.25, where the method of detection is immunoscintigraphy or positron emission tomography.

31. The method according to PP, 25, or 28, in which the disease state is a cancer.

32. The method according to p, in which the cancer is a prostate cancer or running metastatic cancer.

33. The method of determining prognosis for a subject suffering from prostate cancer, comprising control for prostate cancer with the aid of the completion method according to clause 29, where the increase in the number of RG1 polypeptide having the amino acid sequence shown in SEQ ID NO: 2, the same subject at different times is an indicator of poor prognosis.

34. The method according to p or 29, where the biological sample is serum, blood, urine, prostate tissue, or tissue, which is tissue of the prostate.

35. The method according to item 27, where the detectable marker that is detected is a radioisotope, fluorescent compound, bioluminescent compound, chemiluminescent compound, a metal chelating compound or an enzyme.



 

Same patents:

FIELD: medicine.

SUBSTANCE: recombinant strain Escherichia coli is produced, which contains plasmid pHINS21 (Escherichia coli JM109/ pHINS21), defining synthesis of hybrid protein, made of N-terminal fragment of human gamma-interferon and human proinsulin, joined by peptide linker, which contains site of splitting with enterokinase (Asp4Lys). Yield of hybrid product that includes proinsulin, provided with new strain-producer, makes at least 30% of total amount of cell protein. Method is suggested for preparation of human proinsulin, including cultivation of strain-producer Escherichia coli JM109/pHINS21, separation of inclusion bodies and their dissolution, renaturation of hybrid protein and its cleaning with ion-exchange chromatography, splitting of hybrid protein with enterokinase or its catalytic subunit and cleaning of proinsulin by ion-exchange chromatography on sorbates with sulfprofile groups.

EFFECT: invention simplifies technological process for production of recombinant human proinsulin and improves conditions of its execution from the point of view of safety engineering.

4 cl, 4 dwg, 5 ex

FIELD: medicine.

SUBSTANCE: protein is constructed, which includes DNA-binding domain SSBTne from thermophile microorganism Termatoga neapolitana, connected to C-end of domain VirD2 from Agrobacterium tumefaciens, which is a signal of nuclear localisation.

EFFECT: efficient transport of transgene into cell nucleus.

6 dwg, 1 tbl

FIELD: medicine.

SUBSTANCE: method is suggested for production of antibody for binding to NK-cells, which crossly interacts with products of gene KIR2DL1 and KIR2DL2/3 and neutralises inhibitor activity of such KIR. Mentioned method includes selection of such antibodies that crossly interact at least with products of gene KIR2DL1 and KIR2DL2/3, are able to restore lysis with NK cells Cw3+ or Cw4+ target cells and are bound with NK cells or polypeptide of KIR primate. Antibodies produced by this method are described, as well as their derivatives, where antibody is linked with toxin, radionuclide, recognisable aggregation, solid carrier or polyethylene glycol.

EFFECT: invention provides for preparation of single type of antibodies, which controls activity of NK cells of various type, provides for amplification of their cytotoxicity, which may find application in therapy, for increase of activity or cytotoxicity of NK cells in individuals without preliminary detection of HLA type in individual.

7 cl, 13 dwg, 4 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: there is offered application of humanised fused protein for making a medicine used for stimulation of immune response and stabilisation of disease progressing in patients with GD2-positive tumours. The antibody contains antibody H14.18 caught with surface glycosphingolipid GD2 of human cells, and cytokine IL2. There is disclosed method of increase in ADCC and lysis activity of natural killers in cancer patients by introduction of the fused protein. The invention can be applied in GD2-overexpression cancer therapy.

EFFECT: application of the invention provides low-immunogenicity antibody.

2 cl, 8 dwg, 1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention concerns immunology area. Versions of the artificial fused protein consisting of an antibody (or its fragment) and cytokine, fused through a link peptide are offered. The antibody or its fragment is chosen from an antibody 225, 425, KS 1/4, 14.18, anti-CDx-antibody where x has the whole value 1-25. Each of versions of the fused protein has lowered quantity T-epitopes, at least, in the component of the fused protein presented by an antibody, and as consequence, possesses the lowered adjuvanticity, in comparison with an initial molecule. Identification of T-lymphocyte epitopes is performed by the automated calculation of sizes for the binding centres of class II MHC molecules with the subsequent experimental test of the obtained versions of protein for presence of the lowered adjuvanticity. The automated way of T-epitopes calculation is based on use of the Bjom's function modified in such manner that contribution of Van-der-vaals repulsion and lipophilic interaction in pairs between all lipophilic atoms of the chosen segments of the fused protein and a binding groove of a MHC P molecule is taken into account. Also a way of protein construction on the basis of the modified function Bjom's function with the subsequent experimental test of the received versions for presence of the lowered adjuvanticity is revealed, and also application of the fused protein for preparation of a pharmaceutical composition for tumour treatment is in addition considered.

EFFECT: invention use allows obtaining the fused proteins with the lowered adjuvanticity and, basically, keeping identical biological activity in comparison with a parent molecule; it can be used in treatment of tumours.

4 cl, 6 dwg, 22 tbl, 19 ex

FIELD: chemistry, medicine.

SUBSTANCE: claimed is novel hybrid protein CFP10-ESAT6 from M. tuberculosis, inducing reaction of hypersensitivity of delayed type with respect to M. tuberculosis. Chimeric NA, coding claimed protein is described. Described is method of obtaining claimed protein by cultivating cells of strain BL21(DE3) E.Coli, transformed with constructed recombinant expression vector on the basis of plasmid pET22b(+). Claimed is dosed medicinal form, containing claimed protein, for intracutaneous injection for diagnostics of tuberculosis infection.

EFFECT: high output of protein CFP10-ESAT6, which possesses specific immunogenicity.

8 cl, 2 dwg, 7 tbl, 3 ex

FIELD: genetic engineering.

SUBSTANCE: invention refers to genetic engineering and can be used in medical and biologic industry for making recombinant heterocarpine that is an antagonist of human release factor of growth hormone (GHRH). There is disclosed complete nucleotide sequence coding polypeptide heterocarpine; there are disclosed the related primer sequences to be used in heterocarpine gene cloning, as well as genetic make-ups including specified sequence, particularly hybrid gene coding fused protein containing polypeptide heterocarpine, as well as expression vectors for said hybrid gene. There is described method for making recombinant heterocarpine as His-tag fused protein, providing application of the host cells transformed or transfected with the disclosed genetic make-ups.

EFFECT: recombinant heterocarpine according to the invention can be used in making a medicinal agent for cancer treatment.

9 cl, 6 ex

FIELD: medicine.

SUBSTANCE: polypeptides include single-domain antibody against vWF, A1 domain of vWF, A1 domain of activated vWF, A3 domain of vWF, gp1b and/or collagen. Invention claims methods of obtaining indicated polypeptides, methods of coating devices applied in medical practice (e.g. in X-ray structural analysis, endoprosthetics) with indicated polypeptides.

EFFECT: obtainment of polypeptides for treatment of diseases requiring modulation of thrombocyte-mediated aggregation.

40 cl, 69 ex, 30 dwg, 32 tbl

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to field of biotechnology and immunology. Described is physiologically active protein conjugate. Protein conjugate includes physiologically active polypeptide, which is covalently connected with Fc fragment of immunoglobulin by means of polyethylene glycol. Described is method of obtaining protein conjugate. It can find application in production of various polypeptide medications of prolonged action.

EFFECT: increased physiological activity in vivo construction in comparison with native physiologically active polypeptide and increase of half-life in serum of physically active polypeptide with minimal risk of inducing undesirable immune response.

17 cl, 18 dwg, 8 ex

FIELD: medicine.

SUBSTANCE: method of augmentation of duration of action of physiologically active polypeptide in vivo is described. Physiologically active polypeptide is conjugated with Fc fragment of immunoglobulin by means of PEG. Invention use, in comparison with native physiologically active polypeptide, provides the raised physiological activity in vivo designs and-or augmentation of time of a semilife in Serum of physiologically active polypeptide with the minimum risk of induction of undesirable immune responses.

EFFECT: possibility of application of bond at manufacturing of various polypeptides medicinal preparations of the prolonged action.

11 cl, 18 dwg, 8 ex

FIELD: medicine.

SUBSTANCE: there is offered application of humanised fused protein for making a medicine used for stimulation of immune response and stabilisation of disease progressing in patients with GD2-positive tumours. The antibody contains antibody H14.18 caught with surface glycosphingolipid GD2 of human cells, and cytokine IL2. There is disclosed method of increase in ADCC and lysis activity of natural killers in cancer patients by introduction of the fused protein. The invention can be applied in GD2-overexpression cancer therapy.

EFFECT: application of the invention provides low-immunogenicity antibody.

2 cl, 8 dwg, 1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention concerns immunology area. Versions of the artificial fused protein consisting of an antibody (or its fragment) and cytokine, fused through a link peptide are offered. The antibody or its fragment is chosen from an antibody 225, 425, KS 1/4, 14.18, anti-CDx-antibody where x has the whole value 1-25. Each of versions of the fused protein has lowered quantity T-epitopes, at least, in the component of the fused protein presented by an antibody, and as consequence, possesses the lowered adjuvanticity, in comparison with an initial molecule. Identification of T-lymphocyte epitopes is performed by the automated calculation of sizes for the binding centres of class II MHC molecules with the subsequent experimental test of the obtained versions of protein for presence of the lowered adjuvanticity. The automated way of T-epitopes calculation is based on use of the Bjom's function modified in such manner that contribution of Van-der-vaals repulsion and lipophilic interaction in pairs between all lipophilic atoms of the chosen segments of the fused protein and a binding groove of a MHC P molecule is taken into account. Also a way of protein construction on the basis of the modified function Bjom's function with the subsequent experimental test of the received versions for presence of the lowered adjuvanticity is revealed, and also application of the fused protein for preparation of a pharmaceutical composition for tumour treatment is in addition considered.

EFFECT: invention use allows obtaining the fused proteins with the lowered adjuvanticity and, basically, keeping identical biological activity in comparison with a parent molecule; it can be used in treatment of tumours.

4 cl, 6 dwg, 22 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: proposed is a recombinant single-strand trispecific antibody for treating tumours which express CEA. The said antibody consists of a series of three antibody fragments: anti-CEA-scFv, anti-CD3-scFv and VH CD28-antibody, linked by two intermediate linkers (intermediate linker Fc and intermediate linker HSA). If necessary, a c-myc-mark or (His)6-mark can be added at the C-end. Described is DNA, which codes the antibody, expression vector based on it and E.coli cell, containing the vector.

EFFECT: use of the invention is more beneficial in clinical use compared to bispecific antibodies and known trispecific antibodies, makes easier clearing and expression of an antibody, which can further be used in treating CEA-mediated tumours.

10 cl, 21 dwg, 11 ex

FIELD: medicine.

SUBSTANCE: versions of the bond intended for linkage with the external domain B (ED-B) of a fibronectin are offered. The bond includes an antigen-binding fragment of one-chained antibody L19 and a cysteinum-containing linker for hanging of a radioactive label. Versions of a pharmaceutical composition for diagnostics and treatment of angiogenic diseases on the basis of the specified bond are opened. Application of bond for linkage with radioactive bond is described. The method of reception of bond in eucariotic cells is opened, including in Pichia pastoris and a set for reception is radioactive labelled agents on the basis of bond.

EFFECT: high-avid bond accumulation in solid tumours.

23 cl, 4 dwg, 5 tbl, 15 ex

FIELD: immunology, antibodies.

SUBSTANCE: invention elates to human monoclonal antibodies to MN and antibody fragments to MN that are targeted to repeat sequence GEEDLP within proteoglycan domain. Binding with a desired epitope is confirmed by competitive immunoenzyme analysis method ELISA wherein ELISA signal is attenuated in combined incubation with peptide comprising this repeat sequence (PGEEDLPGEEDLP). Binding inhibition can be confirmed by the Biacore study also wherein binding required antibodies with immobilized MN or proteoglycan peptides can be inhibited by peptide repeat sequence. In addition to binding with human peptide repeat sequence anti-MN can inhibit adhesion of CGL-1 cells to plastic plates covered by MN. Human antibodies anti-MN can be used in treatment of cancer diseases or for diagnosis of cancer diseases wherein the level of MN is increased.

EFFECT: valuable medicinal properties of antibodies.

11 cl, 8 dwg, 2 tbl, 13 ex

FIELD: oncology and biotechnology.

SUBSTANCE: invention concerns conjugates used for treatment of malignant tumor. Conjugate includes staphylococcal or streptococcal wild-type superantigen or modified superantigen and antibody constituent. Bacterial superantigen is modified to reduce serum reactivity with preserved its antigenic activity. Amino acid sequence of superantigen incorporates A-E regions determining binding to TCR and MHC molecules class II. Invention is directed to preparing antitumor drug and also to preparing pharmaceutical composition.

EFFECT: use of the conjugate according to invention activate immune system and, therefore, resistance of mammalian against malignant tumor.

67 cl, 11 dwg, 1 tbl, 11 ex

FIELD: biotechnology, peptides.

SUBSTANCE: invention relates to a method for preparing antibodies raised to human leukocyte differentiation factor (HLDF) or to HLDF fragment (31-38) representing peptide of the following structure: Arg-Arg-Trp-His-Arg-Leu-Glu-Lys possessing with antigenic and nucleic acids-hydrolyzing properties, and for diagnostic aims also. Antibodies are prepared from rabbit plasma blood immunized with three injections of antigens wherein synthetic HLDF factor or conjugate is used as antigens. Diagnosis of anaplastic state of human cells is carried out by using solutions of antibodies to HLDF factor or HLDF fragment (31-38) in the concentration 0.0013 mg/ml as biological markers. Invention provides carrying out the differential diagnosis of tumors and normal organs and effective detecting initial stages in cell differentiation disturbances.

EFFECT: improved preparing method of antibody, improved method for diagnosis.

6 cl, 21 dwg, 1 tbl

FIELD: medicine, oncology, biochemistry.

SUBSTANCE: invention relates to fused proteins, namely to the multifunctional fused protein cytokine-antibody. This fused protein involves immunoglobulin region and cytokine fused protein of the formula IL-12-X or X-IL-12 wherein interleukin-12 (IL-12) represents the first cytokine and X represents the second cytokine taken among the group comprising IL-2, IL-4 and GM-CSF bound covalently either by amino-end or carboxyl-end to subunit p35 or p40 of interleukin-12 (IL-12) in its heterodimeric or a single-chain form. Indicated fused cytokine protein is fused by either its amino-end or carboxyl-end with indicated region of immunoglobulin. Multifunctional fused protein cytokine-antibody shows an anticancer activity.

EFFECT: valuable medicinal properties of protein complexes.

13 cl, 40 dwg, 18 ex

The invention relates to the field of immunobiotechnology and may find application in medicine

FIELD: medicine.

SUBSTANCE: invention refers to antibody specifically getting bound with PRO87299 version. In addition, the antibody according to the invention has ability to block interaction HVEM and PRO87299 and to function as PRO87299 agonist. The antibody of agonist nature is produced by hybridoma Btig5F5.1 or Btig3B1.9. For the antibody, there is established amino acid sequence given in the description. The invention discloses the methods of using the antibodies to stimulate or reduction of immune response in immune-associated diseases connected, to relieve lymphoma, and inflammatory disease in requiring mammal, to detect polypeptide PRO87299 in a sample and to manage rejection of grafted cells.

EFFECT: antibody is an immunomodulator that allows applying therapeutically identical medicinal agents both to intensify and reduce immune response.

16 cl, 34 dwg, 7 tbl, 20 ex

Up!