Monoclonal antibodies in diagnosis and therapy
Article Abstract:
A review is presented of the ways monoclonal antibodies are prepared for clinical use and of their effectiveness in diagnosing and treating disease. A monoclonal antibody is a protein produced by a cell of the immune system or by a genetically altered bacterium in response to a particular antigen (another protein). As such, it binds specifically to only that antigen and can, in theory at least, inactivate or enhance its activity. Examples of the conditions in which monoclonal antibodies have been used include autoimmune diseases, graft versus host disease, graft rejection, and certain viral infections. The targets on cell surfaces that serve as antigens are outlined; the CD3 antigen on T cells (the main cell type of the cellular immune system) is the target against which the monoclonal antibody OKT3 is directed. This is the monoclonal antibody in widest clinical use, and OKT3 is currently licensed for treating acute kidney graft rejection. Genetically engineered monoclonal antibodies combine regions of the mouse antibody with regions of the human antibody to maximize effectiveness. Such combinations have been tested against the antigens present on tumors. Problems in developing these agents are briefly discussed. Researchers are trying to produce human monoclonal antibodies by fusing mouse cells and human cells, or by DNA polymerase chain reaction technology (which allows copying antibody-producing genes). However, these monoclonal antibodies have not yet been tested in clinical trials. Antibodies have also been used to carry toxins or cell-killing (cytotoxic) drugs to specific targets on ceratin cells, such as tumor cells. A ''label'' that can be attached to antibodies is radioactivity (in the form of a radionuclide); then, when the antibody binds to its antigen located on, for instance, a tumor cell, it releases local radioactivity that kills the cell. Future clinical uses of monoclonal antibodies are described. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Science
Subject: Science and technology
ISSN: 0036-8075
Year: 1991
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Neutralization of divergent HIV-1 isolates by conformation-dependent human antibodies to gp120
Article Abstract:
Several genetic variants (isolates) of human immunodeficiency virus type 1 (HIV-1), which causes AIDS, are known to exist. An effective vaccine against the disease should protect against a broad range of these variants. A glycoprotein present in the viral envelope, called gp120, elicits antibodies that neutralize the virus, but the antibodies elicited by immunization with one isolate usually cannot neutralize other HIV-1 isolates. This is because the main sites recognized by the neutralizing antibodies lie in a certain region of the gp120 protein called the principal neutralizing determinant (PND), located within the V3 region. However, sera from people infected with HIV-1 can neutralize a broader range of viral isolates, suggesting that antibodies against variants of HIV-1 that differ in shape (conformational epitopes) are present. These epitopes are missing in standard gp120 vaccines and cannot elicit an immune response, which could explain why the spectrum of action of such vaccines is limited. To test this hypothesis, purified antibodies against specific conformations of the gp120 molecule were prepared from human sera and tested for their abilities to neutralize HIV isolates, including isolates with different amino acid sequences in the V3 region. Results indicated that at least three kinds of neutralizing antibodies are present in the sera of humans infected with HIV-1: antibodies against the V3 region (linear antigenic determinants); against gp120 conformational epitopes; and against other structural forms of gp120 (such as oligomers) or epitopes of other viral proteins. The results have implications for the design of effective vaccines against HIV-1, which should contain both linear and conformational epitopes of the gp120 protein. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Science
Subject: Science and technology
ISSN: 0036-8075
Year: 1991
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Monoclonal antibodies at age 20: promise at last?
Article Abstract:
Monoclonal antibodies have yet to become the 'magic bullets' against cancer as many had hoped as early as 1984. But new research brings hope that monoclonal antibodies still hold great potential for treating cancers. Several examples are discussed.
Publication Name: Science
Subject: Science and technology
ISSN: 0036-8075
Year: 1995
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