# Oncolytic viruses

Source: https://onco.cc/technologies/oncolytic-virus/  
OnCo record `oncolytic-virus` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Viruses engineered to infect and burst cancer cells while leaving normal cells alone, and to alert the immune system in the process.

## Summary

A healthy cell that detects a virus mounts an interferon response: it slows its own machinery, calls the immune system and kills itself before the virus spreads. Many cancer cells have already broken parts of that response, because it also restrains growth, and a virus can exploit the break. Stojdl and colleagues showed this directly in 2000 with vesicular stomatitis virus, which killed human tumour lines at interferon doses that fully protected normal cells. Coffey and colleagues showed in 1998 that reovirus needs an activated Ras pathway, which many cancers supply. Martuza and colleagues had already built the first engineered version in 1991, a herpes virus with thymidine kinase deleted so it could only replicate where the host cell supplied the missing function.

Four replicating oncolytic viruses have an approval somewhere. H101 (Oncorine) in China from 2005, on a 160-patient randomised trial reporting response rate and no survival data. Talimogene laherparepvec (Imlygic, HSV-1) from 2015 in melanoma: durable response rate 16.3 per cent against 2.1 per cent for granulocyte-macrophage colony-stimulating factor, with a median overall survival difference of 23.3 against 18.9 months that did not reach significance. Teserpaturev (G47 delta, Delytact) conditionally approved in Japan in 2021 on a single-arm trial of 19 patients with recurrent glioblastoma. Vusolimogene oderparepvec (Tudriqev, RP1), an HSV-1 carrying GM-CSF and a fusogenic protein, given accelerated approval with nivolumab for anti-PD-1-failed melanoma on 6 August 2026, on a 140-patient single-arm cohort with a 32.9 per cent response rate in which uninjected lesions responded too.

Two products often counted in the class are not replicating viruses at all. Nadofaragene firadenovec (Adstiladrin) is a replication-deficient adenovirus that delivers the interferon alfa-2b gene to the bladder lining, and aglatimagene besadenovec (CAN-2409) is a replication-defective adenovirus delivering a prodrug-converting enzyme. They are gene delivery, not oncolysis, and the distinction matters when reading claims about the class. Cretostimogene grenadenorepvec, which does replicate, reported a 75 per cent complete response rate in BCG-unresponsive bladder cancer with carcinoma in situ in a single-arm phase 3 trial.

The randomised record is poor. Adding talimogene laherparepvec to pembrolizumab in melanoma (MASTERKEY-265) did not improve progression-free or overall survival. Toca 5 in recurrent high-grade glioma and PHOCUS in liver cancer were both negative, PHOCUS worse than its control. The unsolved problems are the ones named in 2012: delivery to tumours that cannot be injected, pre-existing and rapidly rising neutralising antibody, the conflict between letting the virus spread and wanting an immune response, and manufacturing yield.

## Fields

- Kind: Technology
- Status: approved
- Last checked: 2026-09-04
- Also known as: Oncolytic virus; Oncolytic virotherapy
- Principle: An attenuated or naturally tumour-selective virus replicates in tumour cells whose antiviral signalling is defective, lyses them, and releases tumour antigens, viral pathogen-associated patterns and any encoded transgene into the tumour, converting lysis into an in situ immunisation.
- Since: 2015
- Strengths: Kills by a mechanism unrelated to chemotherapy or targeted agents, so cross-resistance is unlikely; Toxicity largely does not overlap with other cancer drugs, which is the main argument for combining; Turns dying tumour cells into an antigen source in place, with an encoded adjuvant; Responses in uninjected lesions have been documented, which is evidence of a systemic immune effect
- Limitations: Most products still need a lesion that can be injected; Pre-existing and rapidly rising neutralising antibody blocks intravenous delivery and repeat dosing; Approvals rest on response rates; randomised survival benefit has not been shown; The randomised combination with checkpoint blockade in melanoma was negative; Manufacturing yields are far below what intravenous dosing would need

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Oncolytic_virus
- Wikipedia: https://en.wikipedia.org/wiki/Oncolytic_virus
- Oncolytic virotherapy on OnCo: history, approvals, engineering and failures: https://onco.cc/virotherapy/

## Connected records

- cancers: [Advanced cutaneous squamous cell carcinoma](https://onco.cc/cancers/advanced-cutaneous-scc/), [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Cutaneous squamous cell carcinoma](https://onco.cc/cancers/cutaneous-scc/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Melanoma](https://onco.cc/cancers/melanoma/), [Merkel cell carcinoma](https://onco.cc/cancers/merkel-cell-carcinoma/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/)
- fronts: [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- drugs: [Aglatimagene besadenovec](https://onco.cc/drugs/aglatimagene-besadenovec/), [Cretostimogene grenadenorepvec](https://onco.cc/drugs/cretostimogene/), [H101 oncolytic adenovirus](https://onco.cc/drugs/h101-oncolytic-adenovirus/), [Nadofaragene firadenovec](https://onco.cc/drugs/nadofaragene-firadenovec/), [Olvimulogene nanivacirepvec](https://onco.cc/drugs/olvimulogene-nanivacirepvec/), [Talimogene laherparepvec](https://onco.cc/drugs/talimogene-laherparepvec/), [Vusolimogene oderparepvec](https://onco.cc/drugs/vusolimogene-oderparepvec/)
- companies: [Amgen](https://onco.cc/companies/amgen/), [Candel Therapeutics](https://onco.cc/companies/candel-therapeutics/), [Humane Genomics](https://onco.cc/companies/humane-genomics/), [Kopra Bio](https://onco.cc/companies/kopra-bio/), [Minuteman Therapeutics](https://onco.cc/companies/minuteman-therapeutics/), [Replimune](https://onco.cc/companies/replimune/), [Shanghai Sunway Biotech](https://onco.cc/companies/shanghai-sunway-biotech/), [Takara Bio](https://onco.cc/companies/takara-bio/), [Transgene](https://onco.cc/companies/transgene/)
- people: [Beata Halassy](https://onco.cc/people/beata-halassy/), [Dubravko Forcic](https://onco.cc/people/dubravko-forcic/), [Evanthia Galanis](https://onco.cc/people/evanthia-galanis/), [Howard L. Kaufman](https://onco.cc/people/howard-kaufman/), [Igor Puzanov](https://onco.cc/people/igor-puzanov/), [John C. Bell](https://onco.cc/people/john-bell/), [Kevin Harrington](https://onco.cc/people/kevin-harrington/), [Michael Yu (Yu De-Chao)](https://onco.cc/people/yu-michael/), [Reinhard Dummer](https://onco.cc/people/reinhard-dummer/), [Robert L. Martuza](https://onco.cc/people/robert-martuza/), [Stephen J. Russell](https://onco.cc/people/stephen-russell/), [Tomoki Todo](https://onco.cc/people/tomoki-todo/), [Yuman Fong](https://onco.cc/people/yuman-fong/)
- key papers: [Bischoff 1996: the adenovirus that was said to replicate only where p53 was lost](https://onco.cc/key-papers/paper-bischoff-onyx-015-science-1996/), [Bourgeois-Daigneault 2018: giving the virus before surgery, not after everything else has failed](https://onco.cc/key-papers/paper-bourgeois-daigneault-neoadjuvant-ovt-tnbc-scitranslmed-2018/), [Coffey 1998: reovirus grows in cells with an activated Ras pathway, which describes a great many cancers](https://onco.cc/key-papers/paper-coffey-reovirus-ras-science-1998/), [Hietanen 2022: the marketed oncolytic virus Rigvir was no more oncolytic than any other echovirus isolate](https://onco.cc/key-papers/paper-hietanen-rigvir-echovirus-viruses-2022/), [IGNYTE: an engineered herpes virus with nivolumab in melanoma that had already failed anti-PD-1 therapy](https://onco.cc/key-papers/paper-wong-ignyte-rp1-nivolumab-jco-2025/), [Kelly and Russell 2007: a century of trying to treat cancer with viruses, and why it kept stopping](https://onco.cc/key-papers/paper-kelly-russell-oncolytic-history-moltherapy-2007/), [Martuza 1991: the first genetically engineered virus built to treat a cancer](https://onco.cc/key-papers/paper-martuza-engineered-hsv-glioma-science-1991/), [OPTiM: the trial that made talimogene laherparepvec the first approved oncolytic virus](https://onco.cc/key-papers/paper-andtbacka-optim-talimogene-jco-2015/), [PHOCUS: an oncolytic vaccinia virus before sorafenib in liver cancer did worse than sorafenib alone](https://onco.cc/key-papers/paper-abou-alfa-phocus-pexa-vec-liver-cancer-2024/), [Pugh 2026: should a journal publish a scientist's experiment on herself?](https://onco.cc/key-papers/paper-pugh-self-experimentation-publication-jme-2026/), [Russell 2014: a measles virus given into the vein put one patient's myeloma into complete remission](https://onco.cc/key-papers/paper-russell-mv-nis-myeloma-mayo-2014/), [Russell, Peng and Bell 2012: the field states its own problems](https://onco.cc/key-papers/paper-russell-peng-bell-oncolytic-virotherapy-natbiotech-2012/), [Shalhout 2023: what the approved oncolytic viruses actually do in practice](https://onco.cc/key-papers/paper-shalhout-oncolytic-progress-challenges-natrevclinonc-2023/), [Stojdl 2000: cancer cells that stopped answering interferon cannot stop a virus either](https://onco.cc/key-papers/paper-stojdl-vsv-interferon-defect-natmed-2000/), [The self-experiment: a virologist treated her own recurrent breast cancer with two viruses she made in her own laboratory](https://onco.cc/key-papers/paper-halassy-self-experiment-ovt-vaccines-2024/), [Toca 5: a virus plus a prodrug in recurrent brain cancer, tested properly, and it did not work](https://onco.cc/key-papers/paper-cloughesy-toca5-glioma-jamaoncol-2020/), [Todo 2022: the triple-mutated herpes virus that became Japan's first approved oncolytic virus](https://onco.cc/key-papers/paper-todo-g47delta-glioblastoma-natmed-2022/), [Xia 2004: the randomised trial behind China's approval of the oncolytic adenovirus H101](https://onco.cc/key-papers/paper-xia-h101-head-neck-aizheng-2004/)
- journals: [Cancer gene therapy](https://onco.cc/journals/cancer-gene-therapy/)
- technologies: [Bacteriophage-based tumour delivery](https://onco.cc/technologies/phage-delivery/), [Engineered bacteria as living cancer drugs](https://onco.cc/technologies/engineered-bacteria-therapy/), [In situ vaccination](https://onco.cc/technologies/in-situ-vaccination/), [Intratumoural gene electrotransfer (IL-12 plasmid)](https://onco.cc/technologies/il12-electroporation/), [Viral vector manufacturing (lentiviral, retroviral, AAV)](https://onco.cc/technologies/viral-vector-manufacturing/)
- trials: [A Study of Adjuvant Cretostimogene Grenadenorepvec for Treatment of Intermediate Risk NMIBC Following TURBT](https://onco.cc/trials/nct06111235/), [BOND-003](https://onco.cc/trials/bond-003/), [Phase 2 Study to Evaluate Safety and Efficacy of Cretostimogene Grenadenorepvec in High-Risk NMIBC](https://onco.cc/trials/nct06567743/), [Study of Cretostimogene Given in Patients With Non-Muscle Invasive Bladder Cancer ,Unresponsive to Bacillus-Calmette-Guerin](https://onco.cc/trials/nct07283835/)
- terms: [Cancer vaccines and oncolytic viruses](https://onco.cc/terms/vaccines-and-oncolytic-viruses/), [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Immunogenic cell death](https://onco.cc/terms/immunogenic-cell-death/), [Immunotherapy](https://onco.cc/terms/immunotherapy-term/)
- pairings: [Oncolytic virus + PD-1 blockade](https://onco.cc/pairings/oncolytic-plus-pd1/)
- roadmaps: [Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity](https://onco.cc/roadmaps/immunotherapy-roadmap/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/)
- ideas: [Deliver drugs and cells to the brain through the nose](https://onco.cc/ideas/idea-bio2-intranasal-delivery/), [Make every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours](https://onco.cc/ideas/idea-moon-cold-to-hot-programme/), [Oncolytic viruses that make interleukin-12 only inside the tumour](https://onco.cc/ideas/idea-bio2-oncolytic-regulated-il12/)
- institutions: [Cancer Care Alberta (Alberta Health Services)](https://onco.cc/institutions/cancer-care-alberta/), [Duke Cancer Institute](https://onco.cc/institutions/duke-cancer-institute/), [Nationwide Children's Hospital](https://onco.cc/institutions/nationwide-childrens/), [Society for Immunotherapy of Cancer](https://onco.cc/institutions/sitc/), [The Ottawa Hospital Cancer Centre / Ottawa Hospital Research Institute](https://onco.cc/institutions/ottawa-hospital/), [University Hospital Zurich / Comprehensive Cancer Center Zurich](https://onco.cc/institutions/usz-zurich/)
- pathways: [Cold tumours: immune deserts and exclusion](https://onco.cc/pathways/immune-desert-exclusion/), [The cancer-immunity cycle](https://onco.cc/pathways/cancer-immunity-cycle/)

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