{"entity":{"id":"paper-stojdl-vsv-interferon-defect-natmed-2000","kind":"paper","name":"Stojdl 2000: cancer cells that stopped answering interferon cannot stop a virus either","aka":[],"tldr":"A normal cell warned by interferon shuts a virus down; many cancer cells have broken that alarm to grow, and this paper showed a common animal virus exploits exactly that break.","summary":"Interferons bind cell-surface receptors and set off a signalling cascade that produces both an antiviral state and growth-inhibitory or apoptotic signals. Many cancers acquire mutations in that pathway, which frees them from interferon's growth control. Stojdl and colleagues in John Bell's laboratory argued that the same cells must therefore have given up their antiviral defence, and tested it with vesicular stomatitis virus, an enveloped negative-sense RNA virus that is exquisitely sensitive to interferon.\n\nVesicular stomatitis virus replicated in and killed a range of human tumour cell lines at interferon doses that completely protected normal human primary cultures. A single intratumoural injection reduced tumour burden in nude mice carrying human melanoma xenografts. This is the mechanistic argument the whole field uses in plain words: the virus is not clever, the cancer cell is defenceless.","asOf":"2026-09-25","links":[{"label":"Nat Med 2000","url":"https://doi.org/10.1038/77558"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/10888934/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/10888934"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["john-bell"],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2000,"doi":"10.1038/77558","pmid":"10888934","authors":"Stojdl DF, Lichty B, Knowles S, et al.","paperType":"basic","findings":["Vesicular stomatitis virus replicated in and killed a variety of human tumour cell lines at interferon doses that fully protected normal human primary cell cultures.","A single intratumoural injection reduced tumour burden in nude mice bearing subcutaneous human melanoma xenografts.","The selectivity came from the tumour cells' defective interferon response, not from any engineering of the virus."],"whatItMeans":"This is the reason oncolytic virotherapy is a strategy rather than an accident. Cancer cells frequently disable the interferon response because it restrains their growth, and the same break leaves them unable to mount the antiviral response a healthy neighbour mounts. Everything later in the field, including the choice of which virus to use and which gene to delete, is an attempt to widen that gap.","caveats":["Cell lines and immunodeficient mice. Nude mice lack T cells, so the model measures direct viral killing and cannot show the immune contribution that matters most in patients.","Interferon-pathway defects vary enormously between tumours and are not routinely measured before treatment, so there is still no test that says which patient's cancer is susceptible.","Wild-type vesicular stomatitis virus is neurotoxic in animals by direct routes into the nervous system, which is why the clinical versions are attenuated."]},"route":"/key-papers/paper-stojdl-vsv-interferon-defect-natmed-2000/","neighbours":{"section":[{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}],"person":[{"id":"john-bell","kind":"person","name":"John C. Bell","route":"/people/john-bell/"}],"journal":[{"id":"nature-medicine","kind":"journal","name":"Nature Medicine","route":"/journals/nature-medicine/"}]}}