Intracellular scFvs against the viral E6 oncoprotein provoke apoptosis in human papillomavirus-positive cancer cells.
Fiche publication
Date publication
septembre 2007
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DERYCKERE Francois, Pr ORFANOUDAKIS Georges, Pr WEISS Etienne
Tous les auteurs :
Lagrange M, Boulade-Ladame C, Mailly L, Weiss E, Orfanoudakis G, Deryckere F
Lien Pubmed
Résumé
The E6 protein of human papillomavirus type 16 (16E6) is involved in the tumorigenesis of human cervical cells by targeting numerous cellular proteins. We have designed a strategy for neutralizing 16E6 based on the intracellular expression of single-chain Fv antibodies (scFvs) specific to 16E6. Recombinant adenovirus vectors were constructed to allow expression of two 16E6-binding scFvs and one 16E6-non-binding scFv in HPV16-positive and -negative cells. Expression of the scFvs provoked two types of effects: (i) inhibition of proliferation of all cell lines tested, this aspecific toxicity being likely due to the aggregation of unfolded scFvs; and (ii) apoptosis observed only in HPV16-positive cervical cancer cell lines after expression of 16E6-binding scFvs, this specific effect being proportional to the intracellular solubility of the scFvs. These data demonstrate the feasibility of intracellular immunization with anti-16E6 scFvs and highlight the importance of the solubility of the intracellular antibodies.
Référence
Biochem Biophys Res Commun. 2007 Sep 21;361(2):487-92