Oncolytic adenovirus (OAd) (OAd)

Oncolytic adenoviruses (OAds) are a class of therapeutic agents engineered to selectively infect, replicate within, and destroy malignant cells while sparing healthy tissue. This approach, often referred to as targeting the tumor cell machinery, exploits common genetic aberrations in cancer cells, such as defects in the p53 or Retinoblastoma (Rb) pathways, to facilitate viral replication (Mundstein et al., 2022). Upon infection, the virus hijacks the host cell's metabolic and synthetic processes to produce viral progeny, ultimately leading to immunogenic cell death and the release of new virions to infect adjacent cells. Beyond direct oncolysis, the replication process releases tumor-associated antigens and pathogen-associated molecular patterns (PAMPs), which recruit and activate the host's immune system against the tumor (Baker et al., 2018). Clinical candidates like H101 (Oncorine) and DNX-2401 have demonstrated efficacy in treating solid tumors, although challenges such as pre-existing neutralizing antibodies and systemic toxicity remain significant barriers to widespread use (NIH, 2023). These viruses are frequently modified with tumor-specific promoters or capsid alterations to enhance their selectivity and delivery to metastatic sites.

Other names

Conditionally Replicative AdenovirusCRAdOncolytic adenoviral therapyTumor-selective adenovirusOncolytic adenoviral vector

Oncolytic adenoviruses selectively replicate in cancer cells by exploiting tumor-specific genetic defects, leading to direct cell lysis and the induction of a systemic anti-tumor immune response through the release of tumor antigens and inflammatory signals.