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

## TL;DR

This study shows that an oncolytic adenovirus armed with GM-CSF can boost T-cell infiltration and reduce tumor growth in lung cancer.

## Contribution

The novel contribution is engineering an oncolytic adenovirus with GM-CSF under the E2F promoter to enhance antitumor immunity.

## Key findings

- OAd-Z1 effectively replicates in tumor cells and inhibits tumor growth both in vitro and in vivo.
- The virus promotes T lymphocyte infiltration and induces an abscopal effect.
- OAd-Z1 activates antitumor immune responses and increases cytokine production.

## Abstract

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 adenovirus (OAd) that can directly kill tumor cells in addition to inducing both innate and adaptive immune responses. Therefore, the use of OAd to treat tumors is an appealing approach. In this study, we engineered an OAd armed with a human granulocyte–macrophage colony-stimulating factor (GM-CSF), controlled by the E2F promoter, Ad5/3-E2F-d24-GM-CSF (named OAd-Z1). The antitumor activity of OAd was tested in vitro and in vivo. These findings demonstrated that OAd 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, OAd demonstrated an abscopal effect and stimulated T lymphocyte infiltration in vivo. Our findings demonstrate that OAd-Z1 represents promising immunotherapeutic candidates for lung cancer, with the potential to enhance systemic antitumor immunity.