GM-CSF Armed Oncolytic Adenovirus Enhances T-cell Infiltration and Suppresses Local and Distal Tumor Growth

The limited ability of the immune system to infiltrate solid tumors, attributed to the immunosuppressive tumor microenvironment (TME), remains a significant challenge in cancer therapy Oncolytic adenoviruses (OAds) can directly kill tumor cells in addition to inducing both innate and adaptive immune responses. Therefore, the use of OAds to treat tumors is an appealing approach. In this study, we engineered two OAds armed with a human granulocyte-macrophage colony-stimulating factor (GM-CSF), controlled by E2F or hTERT promoters, Ad5/3-E2F-d24-GM-CSF (named OAd-Z1) or Ad5/3-hTERT-d24-GM-CSF (named OAd-Z2). The antitumor activity of OAds was tested in vitro and in vivo . These findings demonstrated that OAds expressed GM-CSF, replicated effectively in tumor cells, inhibited tumor growth, activated the de novo antitumor response, promoted apoptosis and immunogenic cell death in tumor cells, and increased cytokine and chemokine production both in vitro and in vivo . Additionally, OAds demonstrated an abscopal effect and stimulated T lymphocyte infiltration in vivo . Our findings demonstrate that OAd-Z1 and OAd-Z2 represent promising immunotherapeutic candidates for lung cancer, with the potential to enhance systemic antitumor immunity.