Intracellular scFvs against the viral E6 oncoprotein provoke apoptosis in human papillomavirus-positive cancer cells.

Magali Lagrange (1) , Charlotte Boulade-Ladame (1) , Laurent Mailly (1) , Etienne Weiss (1) , Georges Orfanoudakis (1) , François Deryckere (1)

1 Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique

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.

Domaines: Biologie cellulaire

Magali Lagrange, Charlotte Boulade-Ladame, Laurent Mailly, Etienne Weiss, Georges Orfanoudakis, et al.. Intracellular scFvs against the viral E6 oncoprotein provoke apoptosis in human papillomavirus-positive cancer cells.. Biochemical and Biophysical Research Communications, 2007, 361 (2), pp.487-92. ⟨10.1016/j.bbrc.2007.07.040⟩. ⟨hal-00167371⟩