Thioredoxin scaffolds for therapeutic vaccination

Introduction

The tumor suppressor p16^INK4a is strongly expressed in HPV-transformed precursor lesions and HPV-associated cancer, whereas in normal tissues barely any p16^INK4a (p16) expression is detectable.

In collaboration with Prof. Magnus von Knebel Doeberitz, University Heidelberg and Prof. Simone Ottonello, University of Parma, Italy, we aim to develop a p16-specific vaccine by inserting p16-derived peptides into a scaffold formed by thioredoxin (TRX) of the thermophile Pyrococcus furiosus (Pf). PfTrx has been demonstrated to be an excellent carrier for heterologous antigens (Canali et al., 2014; Rubio et al., 2011; Seitz et al., 2014). Here, we propose to use PfTrx as a carrier for p16 antigens to induce cellular immune responses that are able to prevent or treat growth of p16 positive tumors.

Inserted sequences are restrained by flanking cysteine residues that are forming intramolecular disulfide bonds. Ovalbumin CTL epitope (SIINFEKL, H2Kb restricted) is inserted into pfTrx scaffold as a positive control. The therapeutic efficacy of pfTrx- tumor associated antigen p16 (26 mer) will be studied for HPV-induced intraepithelial neoplasia or derived cancers.