Personalized Cancer Vaccine Platform for Clinically Relevant Oncolytic Enveloped Viruses

Publication year: 2018
Authors: Ylösmäki E. 1, Malorzo C. 1, Capasso C. 1, Honkasalo O. 1, Fusciello M. 1, Martins B. 1, Ylösmäki L. 1, Louna A. 2, Feola S. 1, Paavilainen H. 3, Peltonen K. 1, Hukkanen V. 3, Viitala T. 2, Cerullo V. 4
Affiliations:

1 - Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00790 Helsinki, Finland
2 - Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00790 Helsinki, Finland
3 - Department of Virology, University of Turku, Kiinamyllynkatu 13, 20520, Turku, Finland
4 - Laboratory of Immunovirotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00790 Helsinki, Finland

Published in: Moleuclar Theraphy, 2018, Vol. 9, p. 2315-2325
doi: 10.1016/j.ymthe.2018.06.008

The approval of the first oncolytic virus for the treatment of metastatic melanoma and the compiling evidence that the use of oncolytic viruses can enhance cancer immunotherapies targeted against various immune checkpoint proteins has attracted great interest in the field of cancer virotherapy. We have developed a novel platform for clinically relevant enveloped viruses that can direct the virus-induced immune response against tumor antigens. By physically attaching tumor-specific peptides onto the viral envelope of vaccinia virus and herpes simplex virus 1 (HSV-1), we were able to induce a strong T cell-specific immune response toward these tumor antigens. These therapeutic peptides could be attached onto the viral envelope by using a cell-penetrating peptide sequence derived from human immunodeficiency virus Tat N-terminally fused to the tumor-specific peptides or, alternatively, therapeutic peptides could be conjugated with cholesterol for the attachment of the peptides onto the viral envelope. We used two mouse models of melanoma termed B16.OVA and B16-F10 for testing the efficacy of OVA SIINFEKL-peptide-coated viruses and gp100-Trp2-peptide-coated viruses, respectively, and show that by coating the viral envelope with therapeutic peptides, the anti-tumor immunity and the number of tumor-specific CD8+ T cells in the tumor microenvironment can be significantly enhanced.


MP-SPR keywords: binding affinity and kinetics, cell-penetrating peptide, dissociation rate, envelope virus, herpes simplex virus 1, interaction of peptide and virus, number of peptides bound to one viral particle, SiO2 sensor slides, vaccinia virus