Antigen-capturing oncolytic adenoviruses along with IDO blockade for improved tumor immunotherapy

Through eliciting direct oncolysis, oncolytic viruses (OVs) induce release of tumor proteins, some of which can act as antigens to evoke an antitumor adaptive immune response. However, the poor immunogenicity and utilization efficiency of soluble tumor antigens limit the strength of the activated adaptive immune response and the clinical outcome of OVs. In this study, we found intratumoral injection of oncolytic virus, some of which was drained to the peritumoral lymph nodes. we proposed a strategy to modify oncolytic viruses (OVs) with antigen catchers (polyethylene glycol-linked maleimide) which efficiently capture tumor-derived proteins produced by oncolysis without diminishing its bioactivity of infecting tumor cells, then furtherly triggering enhanced antitumor adaptive immune response. In addition, the surface PEG layer protected AD11-Mal from the pre-exiting anti-AD11 immunity to expand the applicability of AD11-Mal. Finally, we combined AD11-Mal with an indoleamine 2, 3-dioxygenase (IDO) inhibitor 1-methyl-tryptophan (1-MT) to overcome the local negative feedback in tumor immune microenvironment, which combinational regimen induced the long-lasting immune memory to inhibit tumor recurrence. In summary, our strategy greatly enhances the tumor antigen-specific adaptive immunity induced by OV therapy even in the presence of pre-exiting anti-OV immunity, which maybe promising for the development of next-generation OVs.