{"entity":{"id":"paper-bischoff-onyx-015-science-1996","kind":"paper","name":"Bischoff 1996: the adenovirus that was said to replicate only where p53 was lost","aka":[],"tldr":"An adenovirus missing the gene that disables the cell's main tumour suppressor appeared to grow only in cancer cells that had already lost that suppressor, a claim that launched the field's first big clinical programme and was later shown to be the wrong explanation.","summary":"Adenovirus E1B encodes a 55-kilodalton protein that inactivates p53. Bischoff and colleagues showed that a mutant adenovirus lacking it replicated in and lysed p53-deficient human tumour cells but not cells with functional p53, and that putting the 55-kilodalton protein back into the latter made them susceptible. Injection into p53-deficient human cervical carcinomas in nude mice significantly reduced tumour size and completely regressed 60 per cent of tumours.\n\nThe virus became ONYX-015, the most heavily studied oncolytic virus of the 1990s, and later, with a nearly identical design, the Chinese product H101. The tidy mechanism did not survive: O'Shea and colleagues showed in 2004 that selectivity tracks late viral RNA export rather than p53 status, which is why ONYX-015 activity in trials never sorted by p53.","asOf":"2026-09-25","links":[{"label":"Science 1996","url":"https://doi.org/10.1126/science.274.5286.373"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8832876/"},{"label":"O'Shea 2004, the correction to the mechanism (Cancer Cell)","url":"https://doi.org/10.1016/j.ccr.2004.11.012"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["frank-mccormick"],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":1996,"doi":"10.1126/science.274.5286.373","pmid":"8832876","authors":"Bischoff JR, Kirn DH, Williams A, et al.","paperType":"basic","findings":["An adenovirus not expressing the E1B 55-kilodalton protein replicated in and lysed p53-deficient human tumour cells but not cells with functional p53.","Ectopic expression of the 55-kilodalton E1B protein in p53-functional cells made them susceptible to the mutant virus.","Injection into p53-deficient human cervical carcinomas in nude mice reduced tumour size significantly and caused complete regression of 60 per cent of tumours."],"whatItMeans":"This is the paper that made oncolytic viruses look like precision medicine: a named genetic lesion, a virus built to exploit it, a biomarker to select patients. None of that held. It is the field's most useful cautionary tale, because the drug went into large trials on a mechanism that turned out to be wrong, and the selectivity that does exist has never been reducible to one gene.","caveats":["The p53 explanation was overturned. O'Shea and colleagues showed in Cancer Cell in 2004 that late viral RNA export, not p53 inactivation, determines the selectivity of this mutant.","Clinical response to ONYX-015 did not track p53 status in the trials that looked, so the biomarker never worked.","Nude-mouse xenografts of a cervical carcinoma line, with the virus injected directly into an accessible tumour."]},"route":"/key-papers/paper-bischoff-onyx-015-science-1996/","neighbours":{"section":[{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}],"target":[{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"person":[{"id":"frank-mccormick","kind":"person","name":"Frank McCormick","route":"/people/frank-mccormick/"}],"journal":[{"id":"science","kind":"journal","name":"Science","route":"/journals/science/"}]}}