Adjuvant oncolytic virotherapy for personalized anti-cancer vaccination

Abstract

By conferring systemic protection and durable benefits, cancer immunotherapies are emerging as long-term solutions for cancer treatment. One such approach that is currently undergoing clinical testing is a therapeutic anti-cancer vaccine that uses two different viruses expressing the same tumor antigen to prime and boost anti-tumor immunity. By providing the additional advantage of directly killing cancer cells, oncolytic viruses (OVs) constitute ideal platforms for such treatment strategy. However, given that the targeted tumor antigen is encoded into the viral genomes, its production requires robust infection and therefore, the vaccination efficiency partially depends on the unpredictable and highly variable intrinsic sensitivity of each tumor to OV infection. In this study, we demonstrate that anti-cancer vaccination using OVs (Adenovirus (Ad), Maraba virus (MRB), Vesicular stomatitis virus (VSV) and Vaccinia virus (VV)) co-administered with antigenic peptides is as efficient as antigen-engineered OVs and does not depend on viral replication. Our strategy is particularly attractive for personalized anti-cancer vaccines targeting patient-specific mutations. We suggest that the use of OVs as adjuvant platforms for therapeutic anti-cancer vaccination warrants testing for cancer treatment.

Type I interferon-mediated tumor immunity and its role in immunotherapy

“…Moreover, a Maraba-based OV, MAGE-A3, is currently being tested in phase 1/2 studies (NCT02285816/NCT02879760). A recent study suggested that OVs can be co-administered with antigenic peptides in personalized anti-cancer vaccines to target patient-specific mutations [ 106 ]. However, even though OVs have been approved by the FDA and achieved certain efficacy in some patients, the resulting increase in type I IFNs can be problematic.…”

Controlling Cell Trafficking: Addressing Failures in CAR T and NK Cell Therapy of Solid Tumours

“…An alternate use of OV alongside CAR T cell therapy is to utilise genetically modified OVs to induce target antigen expression in the tumour. This has been achieved in solid tumour immunisation regimes via the use of OVs encoding target antigens or by administering the OV alongside antigenic peptides [ 114 , 115 , 116 ]. The ability of these OVs to induce significant antigen-specific T cell responses opens the possibility of using OVs to ectopically express any antigens in tumours in the attempt to aid CAR T cell recognition, solving the problems with suitable antigen choice in solid tumours [ 114 , 115 , 116 ].…”

“…This has been achieved in solid tumour immunisation regimes via the use of OVs encoding target antigens or by administering the OV alongside antigenic peptides [ 114 , 115 , 116 ]. The ability of these OVs to induce significant antigen-specific T cell responses opens the possibility of using OVs to ectopically express any antigens in tumours in the attempt to aid CAR T cell recognition, solving the problems with suitable antigen choice in solid tumours [ 114 , 115 , 116 ]. This principle was demonstrated in preclinical studies, wherein the surface CD19 antigen was delivered by OV vectors to solid tumours, resulting in efficient targeting by anti-CD19 CAR T cell therapy [ 117 , 118 ].…”

The Evolution and Future of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, and Oncolytic Bacteria to the Treatment of Solid Tumors

“…Transgenes are coding sequences engineered to be expressed by oncolytic viruses (and bacteria) for the purpose of modulating cellular gene expression [95]. Examples of transgenes include: cytokines [70], chemokines [87], inhibitors of immune checkpoints [79,104], bi-specific T cell engagers [105,106], tumor antigens [107], and targets for chimeric antigen receptor T cells (CAR-T) [108,109]. Of particular promise is granulocyte-macrophage colony-stimulating factor (GM-CSF) [95,110].…”