Radioconjugation of internalizing antibodies

A - Human Necessities – 61 – K

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A61K 51/10 (2006.01) A61K 49/00 (2006.01)

Patent

CA 2353468

Antibodies to cell surface ligands such as EGFRvIII can be used to therapeutically or diagnosticallly deliver a radiolabel to tumor cells with high selectivity. The utility of radioconjugated internalizing antibodies is limited, however, by release of the label and its reuptake into normal cells. The invention provides new technology for radioconjugation of internalizing antibodies which reduces the release of label and improves retention of radioconjugated antibodies in lysosomes, where radiation is more effectively and selectively delivered to the nucleus of tumor cells.

On peut utiliser les anticorps se fixant aux ligands de surface, comme par exemple les EGFRvIII, pour fournir dans un but thérapeutique ou diagnostique un marqueur radioactif aux cellules tumorales avec une grande spécificité. Cependant, l'utilisation des anticorps d'internalisation radioconjugués est limitée par la libération du marqueur et par son recaptage par les cellules normales. En l'occurrence, cette invention concerne une nouvelle technique de radioconjugaison d'anticorps d'internalisation qui permet de réduire la libération du marqueur et d'augmenter la rétention des anticorps radioconjugués dans les lysosomes, le rayonnement étant appliqué sur les cellules tumorales de façon plus efficace et plus spécifique.

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