Conclusion:In summary, we have been successful in identifying novel, non-peptide small molecule inhibitors of PD1-PDL1 interaction through rational design.Considering their remarkable activity and clinical status, they may present immediate clinical potential against cancers expressing PDL1.They may also prove to be ideal starting points for the design of more potent, selective drug-like inhibitors of PD1-PDL1 interaction.
### A1 Intratumoral immunotherapy. B16-F10 murine melanoma model #### J. Ženka1, V. Caisová1, O. Uher1, P. Nedbalová1, K. Kvardová1, K. Masáková1, G. Krejčová1, L. Paďouková1, I. Jochmanová2, K. I. Wolf3, J. Chmelař1, J. Kopecký1 ##### 1Department of Medical Biology, Faculty of
Aim/Background: To investigate the safety and immune response of fimaVacc-based peptide- and protein antigen vaccination in healthy volunteers. Methods: FimaVacc is a technology that in pre-clinical studies has been shown to increase MHC class I antigen presentation, leading to strongly enhanced cytotoxic- and helper T-cell responses to various types of vaccines. FimaVacc involves formulating the vaccine with a photosensitising compound (fimaporfin) and a toll-like receptor (TLR) agonist, administering the vaccine intradermally, and illuminating the vaccination site the day after vaccine injection. A phase I clinical study in healthy volunteers has been given approval by the authorities in the United Kingdom. In the study, the subjects will be administered two vaccines containing HPV16 E7 peptide antigens or Keyhole Limpet Hemocyanin as models for peptide- and protein-based vaccines. Both antigens will be formulated with the TLR3 agonist poly-ICLC (Hiltonol), and up to three vaccinations will be performed. In addition to assessment of local and systemic adverse effects, cellular and humoral immune responses will be analysed by ELISPOT and ELISA assays, respectively. Results: The principle of the fimaVacc technology will be presented, together with preclinical results showing that fimaVacc strongly enhances both cellular and humoral immune responses and improves anti-tumour effects in different clinically relevant mouse models. The design of the clinical study will also be presented. The clinical study is expected to commence in September 2016, so no clinical results are yet available. Conclusions: The fimaVacc technology strongly enhances the effect of therapeutic cancer vaccines in pre-clinical models. A phase I study in healthy volunteers will start in the very near future. Clinical trial identification: EudraCT number 2016-001023-30 Legal entity responsible for the study: PCI Biotech AS Funding: PCI Biotech AS Disclosure: A. Høgset, T. Otterhaug, L. Wabakken, K. Eivindvik, L. Finnesand, K. Nord, P. Walday: Employed by, and owns stocks in, PCI Biotech AS.