42 research outputs found
CΠΏΠΎΡΠΎΠ±Ρ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΠΈ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Ρ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ Π±ΠΈΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΡΡ Π°Π½ΡΠΈΡΠ΅Π» Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ
Bispecific antibody molecules contain two different antigen-binding centers. Particular interest in bispecific antibodies is due to their therapeutic application. Two preparations of therapeutic bispecific immunoglobulins, approved for use in the US and European countries, are aimed at the treatment of cancer. Studies published in recent years are devoted to various methods of obtaining monoclonal bispecific antibodies, to study their physicochemical properties, biological activity, preclinical and clinical trials. This paper reviews different approachesΒ to the production of antitumor bispecific immunoglobulins, as well as the prospects for their practical application.ΠΠΈΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΡΠΌΠΈ Π½Π°Π·ΡΠ²Π°ΡΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ»Ρ Π°Π½ΡΠΈΡΠ΅Π», ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΠ΅ 2 ΡΠ°Π·Π½ΡΡ
Π°Π½ΡΠΈΠ³Π΅Π½ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΡ
ΡΠ΅Π½ΡΡΠ°. ΠΡΠΎΠ±ΡΠΉ ΠΈΠ½ΡΠ΅ΡΠ΅Ρ ΠΊ ΠΌΠΎΠ»Π΅ΠΊΡΠ»Π°ΠΌ Π±ΠΈΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΡΡ
Π°Π½ΡΠΈΡΠ΅Π» ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½ ΠΈΡ
ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ. ΠΠ²Π° ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π±ΠΈΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΡΡ
ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π»ΠΎΠ±ΡΠ»ΠΈΠ½ΠΎΠ², ΡΠ°Π·ΡΠ΅ΡΠ΅Π½Π½ΡΠ΅ ΠΊ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ Π² Π‘Π¨Π ΠΈ ΡΡΡΠ°Π½Π°Ρ
ΠΠ²ΡΠΎΠΏΡ, Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½Ρ Π½Π° Π»Π΅ΡΠ΅Π½ΠΈΠ΅ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. Π Π°Π±ΠΎΡΡ, ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Π½ΡΠ΅ Π² ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΠ΅ Π³ΠΎΠ΄Ρ, ΠΏΠΎΡΠ²ΡΡΠ΅Π½Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌ ΡΠΏΠΎΡΠΎΠ±Π°ΠΌ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΠΌΠΎΠ½ΠΎΠΊΠ»ΠΎΠ½Π°Π»ΡΠ½ΡΡ
Π±ΠΈΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΡΡ
Π°Π½ΡΠΈΡΠ΅Π», ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΈΡ
ΡΠΈΠ·ΠΈΠΊΠΎ-Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ²ΠΎΠΉΡΡΠ², Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ, Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΈΡΠΏΡΡΠ°Π½ΠΈΡΠΌ. ΠΠ°ΡΡΠΎΡΡΠΈΠΉ ΠΎΠ±Π·ΠΎΡ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°Π΅Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Ρ ΠΊ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
Π±ΠΈΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΡΡ
ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π»ΠΎΠ±ΡΠ»ΠΈΠ½ΠΎΠ², Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Ρ ΠΈΡ
ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ
ΠΠ»Π΅ΡΠ΅Π²ΠΎΠΉ ΡΠ½ΡΠ΅ΡΠ°Π»ΠΈΡ: ΠΈΠΌΠΌΡΠ½ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠ³ΠΎ ΠΏΠ΅ΡΠ΅Ρ ΠΎΠ΄Π° ΠΎΡΡΡΠΎΠΉ ΡΡΠ°Π΄ΠΈΠΈ Π² Ρ ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ Π±ΠΎΠ»Π΅Π·Π½ΠΈ
Several autoimmune diseases with chronic clinical course are characterized by detection of DNA autoantibodies in patientsβ serum, while there are no such IgGs in healthy donorsβ blood or in patients with acute clinical course with no evidence of chronization. Tick-borne encephalitis has not been considered this way. Several strict criteria have been applied to show that the DNase activity is an intrinsic property of IgGs from the sera of TBE patients but not from healthy donors. The relative activity of IgGs has been shown to vary extensively from patient to patient, but most of the preparations (91%) had detectable levels of the DNase activity. Polyclonal DNase IgGs were not active in the presence of EDTA or after a dialysis against EDTA, but could be activated by several externally added metal ions, with the level of activity decreasing in the order Mn2+ + Ca2+ β₯ Mn2+ + Mg2+ β₯ Mn2+ β₯ β₯ Mg2+ + Ca2+ β₯ Ca2+ β₯ Mg2+ > Ca2+, while K+ , Na+ , Ni2+, Zn2+, and Cu2+ did not stimulate DNA hydrolysis. Affinity chromatography on DNA-cellulose separated the DNase IgGs into many subfractions with various affinities for DNA and very different levels of the relative activity. Possible reasons for catalytic diversity of polyclonal human Abzs are discussed.Π ΡΠ΄ Π°ΡΡΠΎΠΈΠΌΠΌΡΠ½Π½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Ρ Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ΠΌ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΡΡΡΡ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΈΠ΅ΠΌ Π² ΠΊΡΠΎΠ²ΠΈ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΠΠΠ°ΡΡΠΎΠ°Π½ΡΠΈΡΠ΅Π», Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ ΠΈΡ
Π½Π΅ ΡΠΎΠ΄Π΅ΡΠΆΠΈΡ ΠΊΡΠΎΠ²Ρ Π·Π΄ΠΎΡΠΎΠ²ΡΡ
Π΄ΠΎΠ½ΠΎΡΠΎΠ² ΠΈΠ»ΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΎΡΡΡΡΠΌ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ΠΌ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, Π½Π΅Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΡΠΌ Π½Π°ΡΡΡΠ΅Π½ΠΈΠ΅ΠΌ ΠΈΠΌΠΌΡΠ½Π½ΠΎΠ³ΠΎ ΡΡΠ°ΡΡΡΠ°, Π±Π΅Π· ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π½ΠΎΠΉ ΡΠΊΠ»ΠΎΠ½Π½ΠΎΡΡΠΈ ΠΊ ΠΏΠ΅ΡΠ΅Ρ
ΠΎΠ΄Ρ Π² Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΏΡΠΎΡΠ΅ΡΡ. ΠΠ»Π΅ΡΠ΅Π²ΠΎΠΉ ΡΠ½ΡΠ΅ΡΠ°Π»ΠΈΡ (ΠΠ) Π½Π΅ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°Π»ΡΡ Ρ ΡΡΠΈΡ
ΠΏΠΎΠ·ΠΈΡΠΈΠΉ. ΠΡΠ΅Π΄Π²Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π΄Π»Ρ Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ ΠΏΠΎΠΈΡΠΊ Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎ ΡΠΎΡΠ½ΡΡ
ΠΊΡΠΈΡΠ΅ΡΠΈΠ΅Π² ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΈΡ ΠΠΠ-Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π°Π½ΡΠΈΡΠ΅Π» ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π»ΠΎΠ±ΡΠ»ΠΈΠ½Π° (Ig) G ΠΈΠ· ΡΡΠ²ΠΎΡΠΎΡΠΊΠΈ ΠΊΡΠΎΠ²ΠΈ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΠ ΠΈ Π·Π΄ΠΎΡΠΎΠ²ΡΡ
Π΄ΠΎΠ½ΠΎΡΠΎΠ². ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½Π°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π°Π½ΡΠΈΡΠ΅Π» IgG Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π²Π°ΡΡΠΈΡΡΠ΅Ρ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², Π½ΠΎ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²ΠΎ ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² (91%) ΠΈΠΌΠ΅Π»ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅ΠΌΡΠΉ ΡΡΠΎΠ²Π΅Π½Ρ ΠΠΠΠ°Π·Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ. ΠΠΎΠ»ΠΈΠΊΠ»ΠΎΠ½Π°Π»ΡΠ½ΡΠ΅ ΠΠΠΠ°Π·Π½ΡΠ΅ Π°Π½ΡΠΈΡΠ΅Π»Π° IgG Π½Π΅ Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π»ΠΈΡΡ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΠΠΠ’Π ΠΈΠ»ΠΈ ΠΏΠΎΡΠ»Π΅ Π΄ΠΈΠ°Π»ΠΈΠ·Π° Ρ ΠΠΠ’Π, Π½ΠΎ ΠΌΠΎΠ³Π»ΠΈ Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°ΡΡΡΡ Π½Π΅ΠΊΠΎΡΠΎΡΡΠΌΠΈ Π΄ΠΎΠ±Π°Π²Π»Π΅Π½Π½ΡΠΌΠΈ ΠΈΠΎΠ½Π°ΠΌΠΈ ΠΌΠ΅ΡΠ°Π»Π»ΠΎΠ² Ρ ΡΡΠΎΠ²Π½Π΅ΠΌ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ, ΡΠΌΠ΅Π½ΡΡΠ°ΡΡΠΈΠΌΡΡ Π² ΡΡΠ΄Ρ Mn2+ + Ca2+ β₯ Mn2+ + Mg2+ β₯ Mn2+ β₯ Mg2+ + Ca2+ β₯ Co2+ β₯ Mg2+ > Ca2+, Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ K+ , Na+ , Ni2+, Zn2+ ΠΈ Cu2+ Π½Π΅ ΡΡΠΈΠΌΡΠ»ΠΈΡΠΎΠ²Π°Π»ΠΈ Π³ΠΈΠ΄ΡΠΎΠ»ΠΈΠ· ΠΠΠ. ΠΡΡΠΈΠ½Π½Π°Ρ Ρ
ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΡ Π½Π° ΠΠΠ-ΡΠ΅Π»Π»ΡΠ»ΠΎΠ·Π΅ ΡΠ°Π·Π΄Π΅Π»ΠΈΠ»Π° ΠΠΠΠ°Π·Π½ΡΠ΅ Π°Π½ΡΠΈΡΠ΅Π»Π° IgG Π½Π° ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²ΠΎ ΡΡΠ±ΡΡΠ°ΠΊΡΠΈΠΉ Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌ ΡΡΠΎΠ΄ΡΡΠ²ΠΎΠΌ ΠΊ ΠΠΠ ΠΈ ΠΎΡΠ΅Π½Ρ ΡΠ°Π·Π½ΡΠΌΠΈ ΡΡΠΎΠ²Π½ΡΠΌΠΈ ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ. ΠΠΎΠ·ΠΌΠΎΠΆΠ½ΡΠ΅ ΠΏΡΠΈΡΠΈΠ½Ρ ΠΊΠ°ΡΠ°Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ°Π·Π½ΠΎΠΎΠ±ΡΠ°Π·ΠΈΡ ΠΏΠΎΠ»ΠΈΠΊΠ»ΠΎΠ½Π°Π»ΡΠ½ΡΡ
ΡΠ΅Π»ΠΎΠ²Π΅ΡΠ΅ΡΠΊΠΈΡ
Π°ΡΡΠΎΠ°Π½ΡΠΈΡΠ΅Π» ΠΎΠ±ΡΡΠΆΠ΄Π°ΡΡΡΡ
Producing and prospects for the use of bispecific antibodies for the treatment of cancer
Bispecific antibody molecules contain two different antigen-binding centers. Particular interest in bispecific antibodies is due to their therapeutic application. Two preparations of therapeutic bispecific immunoglobulins, approved for use in the US and European countries, are aimed at the treatment of cancer. Studies published in recent years are devoted to various methods of obtaining monoclonal bispecific antibodies, to study their physicochemical properties, biological activity, preclinical and clinical trials. This paper reviews different approachesΒ to the production of antitumor bispecific immunoglobulins, as well as the prospects for their practical application
Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis
It was found that high-affinity anti-DNA antibodies were one of the major components of the intrathecal IgG response in multiple sclerosis (MS) patients [Williamson et al., PNAS, 2001]. Recently we have shown that IgGs from the sera of MS patients are active in the hydrolysis of DNA. Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. The relative activities of total protein from sera and CSFs varied remarkably from patient to patient. It was surprising that the specific DNase activity of the total protein of CSF reparations were 198- fold higher than the serum ones. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ,49-fold higher than that from the sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that DNase IgGs of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and MS pathogenesis development.Β© 2014 Parkhomenko et al
CLINICAL AND DIAGNOSTIC SIGNIFICANCE OF DEOXYRIBONUCLEASE ACTIVITY OF POLYCLONAL IgG AND BLOOD SERA IN PATIENTS WITH SPONDYLOARTHRITIS
Abstract. A group of 266 patients with spondyloarthritidis and 69 healthy persons were included in our study. IgG preparations were isolated from blood sera by a combined rivanol/affine chromatography technique. Homogeneity of IgGs was tested by means of SDS-PAGE. Serum samples from patients and healthy persons, and IgG subclasses 1, 2 and 4 were tested for DNAse activity. A method of DNAse activity measurement was based on rivanol capacity to form a clot with DNA. We have found highly significant differences between the levels of DNAse activity associated with IgG preparations and in blood sera from patients with spondyloarthritidis, and healthy donors (p < 0,0001). DNAse activity of IgG and sera in patients with psoriatic arthritis was higher than in patients with reactive arthritis and ankylosing spondylitis (p < 0,0001). Multiple correlations were revealed between DNAse activity of IgG, blood serum, clinical signs of psoriatic arthritis, reactive arthritis, ankylosing spondylitis, and laboratory findings. We have developed novel tests for differential diagnosis between various disorders, e.g., spondyloarthritidis, based on IgG and serum-associated DNAse activity, corresponding to the criteris of useful and very useful diagnostic tests in rheumatology
Characterization and selectivity of catalytic antibodies from human serum with RNase activity.
IgG purified from sera of several patients with systemic lupus erythematosus and hepatitis B are shown to present RNA hydrolyzing activities that are different from the weak RNase A-type activities found in the sera of healthy donors. Further investigation brings evidence for two intrinsic activities, one observed in low salt conditions and another specifically stimulated by Mg2+ions and distinguishable from human sera RNases. Cleavage of RNA substrates by the latter activity is not sequence-specific but sensitive to both subtle conformational and/or drastic folding changes, as evidenced by comparative analysis of couples of structurally well-studied RNA substrates. These include yeast tRNAAsp and its in vitro transcript and human mitochondrial tRNALys-derived in vitro transcripts. The discovery of catalytic antibodies with RNase activities is a first step towards creation of a new generation of tools for the investigation of RNA structure