In vivo antitumor effect of an intracellular single-chain antibody fragment against the E7 oncoprotein of human papillomavirus 16

Luisa Accardi, Francesca Paolini, Angela Mandarino, Zulema Percario, Paola Di Bonito, Valentina Di Carlo, Elisabetta Affabris, Colomba Giorgi, Carla Amici, Aldo Venuti

Research output: Contribution to journalArticle

Abstract

Human papillomavirus (HPV)-associated tumors still represent an urgent problem of public health in spite of the efficacy of the prophylactic HPV vaccines. Specific antibodies in single-chain format expressed as intracellular antibodies (intrabodies) are valid tools to counteract the activity of target proteins. We previously showed that the M2SD intrabody, specific for the E7 oncoprotein of HPV16 and expressed in the endoplasmic reticulum of the HPV16-positive SiHa cells, was able to inhibit cell proliferation. Here, we showed by confocal microscopy that M2SD and E7 colocalize in the endoplasmic reticulum of SiHa cells, suggesting that the E7 delocalization mediated by M2SD could account for the anti-proliferative activity of the intrabody. We then tested the M2SD antitumor activity in two mouse models for HPV tumors based respectively on TC-1 and C3 cells. The M2SD intrabody was delivered by retroviral vector to tumor cells before cell injection into C57BL/6 mice. In both models, a marked delay of tumor onset with respect to the controls was observed in all the mice injected with the M2SD-expressing tumor cells and, importantly, a significant percentage of mice remained tumor-free permanently. This is the first in vivo demonstration of the antitumor activity of an intrabody directed towards an HPV oncoprotein. We consider that these results could contribute to the development of new therapeutic molecules based on antibodies in single-chain format, to be employed against the HPV-associated lesions even in combination with other drugs. What's new Intrabodies, or antibodies that act intracellularly, could be effective for counteracting oncoproteins, such as the E7 oncoprotein of human papillomavirus (HPV). This study shows that the intrabody M2SD co-localizes intracellularly with E7 of HPV16, likely accounting for the intrabody's antiproliferative effects. In vivo antitumor efficacy of M2SD was demonstrated in two HPV animal models, in which tumor onset was delayed. The findings pave the way for the development of a new, intrabody-based therapeutic approach against HPV.

Original languageEnglish
Pages (from-to)2742-2747
Number of pages6
JournalInternational Journal of Cancer
Volume134
Issue number11
DOIs
Publication statusPublished - Jun 1 2014

Keywords

  • cancer therapy
  • E7 oncoprotein
  • human papillomaviruses
  • intrabodies
  • scFv

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Accardi, L., Paolini, F., Mandarino, A., Percario, Z., Di Bonito, P., Di Carlo, V., Affabris, E., Giorgi, C., Amici, C., & Venuti, A. (2014). In vivo antitumor effect of an intracellular single-chain antibody fragment against the E7 oncoprotein of human papillomavirus 16. International Journal of Cancer, 134(11), 2742-2747. https://doi.org/10.1002/ijc.28604