Potentiation of anti-cd38-immunotoxin cytotoxicity

Details Potentiation of anti-cd38-immunotoxin cytotoxicity Potentiation of anti-cd38-immunotoxin cytotoxicity

A - Human Necessities

61

K

A61K 39/395 (2006.01) A61K 38/19 (2006.01) A61K 47/48 (2006.01)

Patent

CA 2358430

The present invention is directed to the use of agents that induce high levels of cell surface molecules to provide targets for immunotoxins directed against the same cell surface molecules. A specific example is given in which all- trans-retinoic acid (RA) is used to induce high levels of CD38 cell surface antigen expression in several myeloid and lymphoid leukemia cells. CD38 was then used as target for delivering plant toxin (gelonin) to leukemia cells. Treatment of leukemia cells with RA induced high levels of CD38 in those cells that otherwise had low CD38 expression. The RA-induced leukemia cells then became exquisitely sensitive to an immunotoxin constructed from an anti-CD38 monoclonal antibody conjugated to the plant toxin gelonin.

La présente invention concerne l'utilisation d'agents induisant de forts taux de molécules de surface cellulaire, pour fournir des cibles aux immunotoxines agissant contre les mêmes molécules de surface cellulaire. On donne un exemple spécifique, dans lequel l'acide tout-trans rétinoïque (RA) est utilisé pour induire de forts taux d'expression d'antigène de surface cellulaire CD38, dans plusieurs cellules leucémiques myéloïdes et lymphoïdes. Le CD38 est ensuite utilisé en tant que cible, pour délivrer de la phytotoxine (gélonine) aux cellules leucémiques. Le traitement des cellules leucémiques avec le RA induit de forts taux de CD38 dans ces cellules, qui, sans ce traitement, présentent une faible expression de CD38. Les cellules leucémiques induites par RA deviennent ensuite extrêmement sensibles à une immunotoxine, formée à partir d'un anticorps monoclonal anti-CD38 conjugué à la phytotoxine gélonine.

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