Tumor cells (oncolytic replication via Ad3 receptor); expresses TNF-alpha and IL-2

Class

Oncolytic adenovirus (serotype 5/3 capsid-modified) expressing TNF-alpha and IL-2 (igrelimogene litadenorepvec)

Pathway

Viral-mediated tumor lysis with TNF-alpha/IL-2-driven tumor microenvironment remodeling and CTL activation

This mechanism describes an oncolytic adenovirus, a virus engineered to preferentially infect and destroy cancer cells rather than healthy tissue. Its outer capsid is a chimera of adenovirus serotypes 5 and 3, which allows the virus to enter cells through the receptor used by serotype 3 rather than the classical adenovirus receptor that many tumors downregulate. This capsid modification broadens the range of tumors the virus can infect. Once inside a cancer cell, the virus exploits defects common in tumor biology, such as disrupted cell-cycle checkpoints, to replicate selectively and eventually rupture the cell, releasing new viral particles and tumor antigens. The construct is further engineered to express two immune-signaling proteins, TNF-alpha and interleukin-2, directly within the tumor. These molecules help convert an immunologically inactive tumor microenvironment into one that attracts and activates cytotoxic T lymphocytes, the immune cells responsible for recognizing and killing cancer cells. This dual action, direct viral lysis combined with local immune activation, is relevant across solid tumor types that resist conventional immunotherapy because they lack sufficient T-cell infiltration or antigen visibility to the immune system.