ABSTRACT
Two monoclonal antibodies recognizing non-overlapping epitopes of the PRAME protein were injected into immunocompetent mice to study their influence on the growth of subcutaneous tumor nodes. The B16F10 murine melanoma line, either expressing human PRAME protein or bearing only a vector without PRAME gene, were used as transplants. Each of the antibodies showed the ability to suppress tumor growth of a PRAME-expressing tumour, but not a tumor without PRAME.
Subject(s)
Antibodies, Monoclonal/pharmacology , Antigens, Neoplasm/immunology , Epitopes/immunology , Melanoma, Experimental/prevention & control , Animals , Antibodies, Monoclonal/administration & dosage , Female , Melanoma, Experimental/etiology , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BLABSTRACT
We investigated the epitope specificity of different monoclonal antibodies recognizing the cancer testis antigen PRAME. Antibody 5D3 binds to the fragment of PRAME corresponding to 160-180 amino acid residues. Antibodies 6H8 and F11 bind to the fragment corresponding to 180-200 amino acid residues of PRAME. These antibodies retained the ability to recognize these PRAME fragments after chimerization.
Subject(s)
Antibodies, Monoclonal/immunology , Antigens, Neoplasm/immunology , Epitopes/immunology , Neoplasms/immunology , Testis/immunology , Animals , Antigens, Neoplasm/metabolism , Cells, Cultured , Cricetinae , Epitopes/chemistry , Epitopes/metabolism , Humans , Male , Mice , Neoplasms/metabolism , Neoplasms/pathology , Testis/metabolismABSTRACT
We generated a novel human neutralizing human mAb RabD4 against rabies virus glycoprotein using in vitro stimulation of human peripheral B cells produced by immunized donor. The human mAb RabD4 showed a high antigen-binding activity and virus-neutralizing activity in the FAVN test with the CVS-11 rabies virus.
Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Rabies virus/immunology , Viral Proteins/immunology , HumansABSTRACT
Rabies virus is a prototypical neurotropic virus that causes one of the most dangerous zoonotic diseases in humans. Humanized or fully human monoclonal antibodies (mAb) that neutralize rabies virus would be the basis for powerful post-exposure prophylaxis of rabies in humans, having several significant benefits in comparison with human or equine rabies polyclonal immunoglobulins. The most advanced antibodies should broadly neutralize natural rabies virus isolates, bind with conserved antigenic determinants of the rabies virus glycoprotein, and show high neutralizing potency in assays in vivo. The antibodies should recognize nonoverlapping epitopes if they are used in combination. This review focuses on basic requirements for anti-rabies therapeutic antibodies. The urgency in the search for novel rabies post-exposure prophylaxis and methods of development of anti-rabies human mAb cocktail are discussed. The rabies virus structure and pathways of its penetration into the nervous system are also briefly described.
Subject(s)
Antibodies, Monoclonal/immunology , Post-Exposure Prophylaxis , Rabies virus/immunology , Animals , Humans , Recombinant Proteins/immunologyABSTRACT
Autoiminune disorders are chronic diseases characterized by abnormal immune response directed against self-antigens that leads to tissue damage and violation of its normal functioning. Such diseases often result in disability or even death of patients. Nowadays a number of monoclonal antibodies to pro-inflammatory cytokines and their receptors are successfully used for the targeted treatment of autoimmune diseases. One of the perspective targets in autoimmune disease therapy is interferon gamma, a key cytokine in Th1 cells differentiation, activation of macrophages, and inflammation. In the present work, 5 monoclonal antibodies to human IFN-γ were obtained. For the development of potential therapeutic agent, we have performed neutralizing activity and affinity analysis of the antibodies. Based on the data obtained, the monoclonal antibody F1 was selected. This antibody has a dissociation constant 1.7 x 10(-9) M and IC90 = 8.9 ± 2.0 nM measured upon antibody inhibition of the IFN-γ-induced HLA-DR expression on the surface of U937 cells. We have constructed a bicistronic vector for the production of recombinant chimeric Fab fragment F1 chim in E. coli cells. The recombinant chimeric Fab fragment Fl chim neutralizes IFN-γ activity in vitro and has a dissociation constant 1.8 x 10(-9) M.
