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. [Display omitted] •The surface Mal modification did not affect the oncolysis activities of AD11.•AD11-Mal captured and drain a myriad of neoantigens to the drained lymph for subsequent activation of antitumor immunity.•AD11-Mal effectively induces tumor antigen-specific immune response in the mice with and without pre-exiting anti-AD11 immunity.•The antitumor effects of AD11-Mal disappeared in the CD8+ T-cell depletion mouse models, indicating that antitumor activity were associated with immune responses.•AD11-Mal + 1-methyl-tryptophan (1-MT) can induce effective immune memory, which is critical for a long-term prevention of tumor recurrence.