Kliniken & Institute ... Institute Pathologisches Institut... Abteilungen Angewandte... Forschung HPV-assoziierte Tumoren... Vakzine

Vaccines against transforming HPV infections

Background

Overexpression of p16INK4a in HPV-transformed cells prompted us to develop vaccines targeting this protein. In normal cells, expression of p16INK4a triggers immediate cell cycle arrest and senescence. HPV-transformed cells however can continue to grow despite overexpression of p16INK4a.

What we do

We therefore hypothesized that using p16INK4a as vaccine target may result in an efficient immune therapy for HPV-associated but presumably also other human cancers.

An initial clinical trial to test this concept showed that p16INK4a-based vaccine can be administered safely without causing severe side effects. It further documented that patients who were vaccinated develop a robust immune response against p16INK4a.

Currently we are extending these initial clinical trials and are actively seeking to improve administration routes and efficacy of this vaccine.

Key publications

  • Reuschenbach M, Pauligk C, Karbach J, Rafiyan MR, Kloor M, Prigge ES, Sauer M, Al-Batran SE, Kaufmann AM, Schneider A, Jäger E, von Knebel Doeberitz M. A phase I/IIa study to test safety and immunogenicity of a p16INK4a peptide vaccine in patients with advanced human papillomavirus-associated cancers. Cancer 2016 May 1;122(9):1425-33. 
  • Prigge ES, Toth C, Dyckhoff G, Wagner S, Müller F, Wittekindt C, Freier K, Plinkert P, Hoffmann J, Vinokurova S, Klussmann JP, von Knebel Doeberitz M, Reuschenbach M. p16(INK4a) /Ki-67 co-expression specifically identifies transformed cells in the head and neck region. Int J Cancer. 2015 Apr 1;136(7):1589-99.
  • Reuschenbach M. [Targeting p16(INK4a) by therapeutic vaccination : Concept and status of clinical investigations in HPV-associated head and neck cancers]. HNO. 2015 Feb;63(2):104-10.
  • Reuschenbach M, Seiz M, von Knebel DC, Vinokurova S, Duwe A, Ridder R, Sartor H, Kommoss F, Schmidt D, von Knebel Doeberitz  M. Evaluation of cervical cone biopsies for coexpression of p16INK4a and Ki-67 in epithelial cells. Int J Cancer 2012 Jan 15;130(2):388-94.
  • von Knebel Doeberitz M, Reuschenbach M, Schmidt D, Bergeron C.Biomarkers for  cervical cancer screening: the role of p16(INK4a) to highlight transforming HPV infections. Expert Rev Proteomics. 2012 Apr;9(2):149-63