Targeted cytolysis of cancer cells

Details Targeted cytolysis of cancer cells Targeted cytolysis of cancer cells

C - Chemistry, Metallurgy

12

N

C12N 15/62 (2006.01) A61K 47/48 (2006.01) A61K 48/00 (2006.01) C07K 14/705 (2006.01) C07K 14/725 (2006.01) C07K 14/73 (2006.01) C07K 16/30 (2006.01) C07K 16/46 (2006.01) C12N 5/10 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2269738

Chimeric proteins and DNA encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to TAG-72 in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signalling pathway. Binding of TAG- 72 to the extracellular domain results in transduction of a signal and activation of a signalling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. The chimeric DNA may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types. A suitable extracellular domain is a single-chain antibody.

Cette invention concerne des protéines chimériques ainsi qu'un ADN codant ces protéines. Ces protéines chimériques se caractérisent par un domaine extra-cellulaire qui est capable de se lier au TAG-72 de manière non restreinte sur le plan de MHC. Ces protéines se caractérisent également par un domaine de trans-membrane et par un domaine cytoplasmique permettant d'activer un trajet de signalisation. La liaison du TAG-72 au domaine extra-cellulaire entraîne la transduction d'un signal et l'activation d'un trajet de signalisation dans la cellule, ce qui permet ensuite d'induire la cellule afin d'effectuer diverses fonctions ayant trait au trajet de signalisation. L'ADN chimérique peut être utilisé afin de modifier les lymphocytes ainsi que les cellules souches hématopoïétiques servant de précurseurs en un certain nombre de types importants de cellules. Un anticorps à chaîne unique peut jouer le rôle de domaine extra-cellulaire acceptable.

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