Oncolytic immunotherapeutics (OIs) are viruses designed to preferentially replicate in and lyse cancer cells, thereby triggering antitumor immunity. Numerous oncolytic platforms are currently in clinical development. Here we review preclinical and clinical experience with Pexa-Vec (pexastimogene devacirepvec, JX-594). Pexa-Vec is derived from a vaccinia vaccine strain that has been engineered to target cancer cells and express the therapeutic transgene granulocyte macrophage colony-stimulating factor (GM-CSF) in order to stimulate antitumor immunity. Key to its ability to target metastatic disease is the evolution of unique vaccinia virus characteristics that allow for effective systemic dissemination. Multiple mechanisms of action (MOA) for Pexa-Vec have been demonstrated in preclinical models and patients: 1) tumor cell infection and lysis, 2) antitumor immune response induction, and 3) tumor vascular disruption. This review will summarize data on the Pexa-Vec MOA as well as provide an overview of the Pexa-Vec clinical development program from multiple Phase I studies, Phase II studies in renal cell cancer and colorectal cancer, through Phase IIb clinical testing in patients with advanced hepatocellular carcinoma (primary liver cancer).
Keyphrases
- cell therapy
- immune response
- phase ii
- clinical trial
- single cell
- small cell lung cancer
- newly diagnosed
- stem cells
- squamous cell carcinoma
- end stage renal disease
- adipose tissue
- randomized controlled trial
- ejection fraction
- dendritic cells
- prognostic factors
- machine learning
- toll like receptor
- case control
- quality improvement
- young adults
- data analysis
- big data
- papillary thyroid
- inflammatory response
- drug induced
- squamous cell
- patient reported
- placebo controlled
- study protocol