Phase I Clinical Study for Validation of Fimaporfin-Based Photochemical Internalisation: A Novel Technology for Enhancing Cellular Immune Responses Important for Therapeutic Effect of Peptide-and Protein-Based Vaccines

Abstract

Abstract Background FimaVacc is a vaccine formulated by the photosensitising compound fimaporfin and a toll-like receptor (TLR) agonist, and is administered intradermally followed by illumination of the vaccination site. In preclinical studies, fimaVacc has been shown to improve MHC class I antigen presentation, resulting in strongly enhanced cytotoxic and helper T-cell responses to various types of peptide and protein vaccines. Methods A phase I clinical study with fimaVacc has been performed in healthy volunteers to study the safety and immunogenicity of this novel vaccine. The subjects were vaccinated with HPV16 E7 peptides and Keyhole Limpet Hemocyanin (KLH) protein, serving as model antigens for peptide- and protein-based vaccines. Both antigens were formulated with fimaporfin and the TLR3 agonist poly-ICLC (Hiltonol) and administered in up to three vaccinations. Local and systemic adverse effects were assessed for safety, and cellular and humoral immune responses were analysed by ELISPOT, flow cytometry and ELISA assays to determine the immunogenicity of fimaVacc. 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 mouse models. The clinical study showed that intradermal vaccination with fimaVacc was well tolerated, with no systemic side effects and generally only mild local reactions. Elispot analysis showed that fimaVacc can significantly increase the number of healthy donors displaying a T-cell response to HPV peptide vaccination. Furthermore, Elispot and flow cytometry analyses demonstrated an enhancement of both HPV-specific CD4+ and CD8+ T cells upon fimaVacc treatment. Conclusion The photochemically based fimaVacc vaccination technology can be applied safely in humans, and enhances T-cell responses to an HPV peptide vaccine over what is achieved in a control group which received antigen + adjuvant without fimaVacc. Clinical trial identification NCT02947854. Legal entity responsible for the study PCI Biotech AS. Funding PCI Biotech AS. Disclosure S. Janetzki: Advisory / Consultancy: PCI Biotech AS. V.T. Edwards: Full / Part-time employment: PCI Biotech AS. H. Olivecrona: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: PCI Biotech AS. S.H. van der Burg: Advisory / Consultancy: PCI Biotech AS. T. Otterhaug: Shareholder / Stockholder / Stock options, Full / Part-time employment: PCI Biotech AS. A. Hogset: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: PCI Biotech AS. All other authors have declared no conflicts of interest.