A new kind of antibody treatment has eliminated Ebola in several monkeys, yielding promise for a forthcoming vaccine. No cure currently exists for Ebola, and conventional treatments need to be administered within an hour of infection, a somewhat impractical solution given that symptoms may only appear after several days. Researchers from the Public Health Agency of Canada and the University of Manitoba used a more effective and expensive technique to get antibodies cloned from a single cell line, producing what are called monoclonal antibodies.
Finally, heavy and light chain sequences are paired and expressed as recombinant monoclonal antibodies. Using this technology, we isolated monoclonal antibodies for five antigens from the sera of immunized rabbits and mice. The antigen-specific activities of the monoclonal antibodies recapitulate or surpass those of the original affinity-purified polyclonal antibodies. This technology may aid the discovery and development of vaccines and antibody therapeutics, and help us gain a deeper understanding of the humoral response.
Immunogenicity is a major limitation to therapy with certain monoclonal antibodies and proteins. A major driver for immunogenicity is the presence of human T-cell epitopes within the protein sequence which can activate helper T-cells resulting in the sustained production of antibodies and neutralization of the therapeutic effect. Deimmunization is a new technology for location and removal of T-cell epitopes through the combined use of immunological and molecular biology techniques. In the case of deimmunization of antibodies, mutations to remove T-cell epitopes can generally be introduced without significantly reducing the binding affinity of the antibody.
Monoclonal antibodies have great potential as a unique set of highly specific reagents for the prophylaxis, diagnosis and therapy of human diseases. However, a major problem encountered is the immunogenicity of these murine antibodies which limits their usefulness. In addition, human antibodies may be more efficient than mouse antibodies in mediating biological effector functions such as antibody-dependent cellular cytotoxicity in human patients.
Far from being overly grandiose, Levy's intuition was too limited. His finding -- that it was possible to generate monoclonal antibodies that would specifically recognize cancer cells inside the body and tag them for destruction -- paved a new direction in the field of oncology and the treatment of thousands of cancer patients.
The terms "antibody" and "monoclonal antibody" (mAb) may be used interchangeably and refer to intact immunoglobulins produced by hybridomas, immunoconjugates and, as appropriate, immunoglobulin fragments and recombinant proteins derived from immunoglobulins, such as chimeric and humanized immunoglobulins, F(ab') and F(ab')2 fragments, single-chain antibodies, recombinant immunoglobulin variable regions (Fvs) etc.
Monoclonal antibodies (mAbs) have become vitally important to modern medicine and are currently one of the major biopharmaceutical products in development. However, the high clinical dose requirements of mAbs demand a greater biomanufacturing capacity, leading to the development of new technologies for their large scale production, with mammalian cell culture dominating the scenario. Although some companies have tried to meet these demands by creating bioreactors of increased capacity, the optimization of cell culture productivity in normal bioreactors appears as a better strategy.
Monoclonal antibodies possess many qualities such as high target-selectivity, the ability to initiate immune recognition of the target, and long circulation half lives that make them attractive molecules for therapeutic development. The initial drawbacks with antibodies derived from immunized mice were overcome by humanization and, more recently, by the generation of fully human antibodies.
The monoclonal antibodies are capable of distinguishing molecules with even subtle chemical differences, such as the difference of just a single amino acid in the sequence of hundreds within a substance. Because the monoclonal antibody technique allows scientists to make pure antibodies against any chosen antigen, Dr. Milstein has also said that ''it is somewhat like selecting individual dishes out of a very elaborate menu: antibodies a la carte.''
Monoclonal antibodies are created by first immunizing an animal (typically a mouse) with the antigen of interest, harvesting its spleen after determination of successful polyclonal antibody production, fusion of splenic cells in vitro with an immortalized cell line and then subsequent production of large amounts of monoclonal antibodies either in vivo or in vitro. Development of a suitable hybridoma cell line and subsequent monoclonal antibody production has the capacity to cause inflammation, tissue necrosis, discomfort, pain and potentially death in the mouse.