Trans-membrane-antibody induced inhibition of apoptosis

Details Trans-membrane-antibody induced inhibition of apoptosis Trans-membrane-antibody induced inhibition of apoptosis

C - Chemistry, Metallurgy

07

K

C07K 19/00 (2006.01) A61K 38/10 (2006.01) A61K 39/104 (2006.01) A61K 39/395 (2006.01) A61K 47/42 (2006.01) A61K 47/48 (2006.01) A61K 51/10 (2006.01) C07K 7/08 (2006.01) C07K 16/40 (2006.01) G01N 33/566 (2006.01)

Patent

CA 2518119

Cell suicide (apoptosis) is associated with pathogenesis, for example, it is the major cause for the loss of neurons in Alzheimer's disease. Caspase-3 is critically involved in the pathway of apoptosis. Superantibody (SAT)-trans- membrane technology has been used to produce antibodies against the caspase enzyme in an effort to inhibit apoptosis in living cells. The advantage of using trans-membrane antibodies as apoptosis inhibitors is their specific target recognition in the cell and their lower toxicity compared to conventional apoptosis inhibitors. It is shown that a MTS-transport-peptide modified monoclonal anti-caspase-3 antibody reduces actinomycin D-induced apoptosis and cleavage of spectrin in living cells. These results indicate that antibodies conjugated to a membrane transporter peptide have a therapeutic potential to inhibit apoptosis in a variety of diseases.

La mort cellulaire (apoptose) est associée à la pathogénèse, par exemple, sa cause principale de perte de neurones dans la maladie d'Alzheimer. La Caspase-3 est impliquée de manière critique dans la voie de l'apoptose. La technologie de superanticorps transmembranaires (SAT) sert à produire des anticorps dirigés contre l'enzyme caspase dans un effort d'inhiber l'apoptose dans les cellules vivantes. L'avantage d'utiliser les anticorps transmembranaires comme inhibiteurs de l'apoptose tient au fait qu'ils permettent de reconnaître une cible spécifique dans la cellule et qu'ils font preuve d'une faible toxicité par rapport aux inhibiteurs de l'apoptose habituels. L'invention montre qu'un anticorps anti-caspase-3 monoclonal modifié par peptide de transport MTS réduit l'apoptose induite par l'actynomycine D et le clivage de spectrine dans les cellules vivantes. Ces résultats indiquent que les anticorps conjugués à un peptide transporteur membranaire ont un potentiel thérapeutique permettant d'inhiber l'apoptose dans un grand éventail de maladies.

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