Oncolytic viruses that make interleukin-12 only inside the tumour
Interleukin-12 is one of the most powerful immune stimulants but is too toxic to inject into the bloodstream. A virus can be engineered to make it only inside a tumour.
Systemic interleukin-12 caused severe toxicity in the 1990s and was abandoned. Oncolytic herpes and adenovirus vectors carrying interleukin-12 under regulated or drug-inducible promoters, including trials in recurrent glioblastoma, keep exposure local and measurable. Combining a regulated cytokine payload with checkpoint blockade is a rational path to converting cold tumours.
- Cold tumours and the immunosuppressive microenvironment · Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.
- The brain: barrier and sanctuary · Most drugs cannot cross into the brain, so brain tumours and brain metastases lag every other site.
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