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expected.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"paper-cloughesy-toca5-glioma-jamaoncol-2020","kind":"paper","name":"Toca 5: a virus plus a prodrug in recurrent brain cancer, tested properly, and it did not work","route":"/key-papers/paper-cloughesy-toca5-glioma-jamaoncol-2020/","year":2020,"journal":"JAMA Oncology","paperType":"rct","tldr":"Four hundred people with a brain tumour that had come back were randomly given either a virus-delivered enzyme plus a pill it converts into chemotherapy, or standard treatment; survival was the same.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"paper-bourgeois-daigneault-neoadjuvant-ovt-tnbc-scitranslmed-2018","kind":"paper","name":"Bourgeois-Daigneault 2018: giving the virus before surgery, not after everything else has failed","route":"/key-papers/paper-bourgeois-daigneault-neoadjuvant-ovt-tnbc-scitranslmed-2018/","year":2018,"journal":"Science Translational Medicine","paperType":"basic","tldr":"In mice with triple-negative breast cancer, treating with a cancer-killing virus before the tumour was removed made checkpoint immunotherapy work afterwards, which it otherwise did not.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"paper-andtbacka-optim-talimogene-jco-2015","kind":"paper","name":"OPTiM: the trial that made talimogene laherparepvec the first approved oncolytic virus","route":"/key-papers/paper-andtbacka-optim-talimogene-jco-2015/","year":2015,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Injecting an engineered herpes virus into melanoma lesions produced lasting shrinkage in about one patient in six, compared with one in fifty on the control drug, but it did not clearly help people live longer.","via":[{"id":"talimogene-laherparepvec","kind":"drug","name":"Talimogene laherparepvec","route":"/drugs/talimogene-laherparepvec/"},{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"paper-russell-mv-nis-myeloma-mayo-2014","kind":"paper","name":"Russell 2014: a measles virus given into the vein put one patient's myeloma into complete remission","route":"/key-papers/paper-russell-mv-nis-myeloma-mayo-2014/","year":2014,"journal":"Mayo Clinic Proceedings","paperType":"translational","tldr":"Two people with drug-resistant myeloma were given an enormous dose of engineered measles virus into a vein; both responded and one went into a lasting complete remission.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"paper-russell-peng-bell-oncolytic-virotherapy-natbiotech-2012","kind":"paper","name":"Russell, Peng and Bell 2012: the field states its own problems","route":"/key-papers/paper-russell-peng-bell-oncolytic-virotherapy-natbiotech-2012/","year":2012,"journal":"Nature Biotechnology","paperType":"review","tldr":"The review that set the modern agenda for cancer-killing viruses, and named the four things that had to be solved.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"paper-kelly-russell-oncolytic-history-moltherapy-2007","kind":"paper","name":"Kelly and Russell 2007: a century of trying to treat cancer with viruses, and why it kept stopping","route":"/key-papers/paper-kelly-russell-oncolytic-history-moltherapy-2007/","year":2007,"journal":"Molecular Therapy","paperType":"review","tldr":"The idea that a virus might shrink a tumour is more than a hundred years old; this history explains the early attempts, why they were abandoned, and what changed.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"paper-xia-h101-head-neck-aizheng-2004","kind":"paper","name":"Xia 2004: the randomised trial behind China's approval of the oncolytic adenovirus H101","route":"/key-papers/paper-xia-h101-head-neck-aizheng-2004/","year":2004,"journal":"Ai Zheng (Chinese Journal of Cancer)","paperType":"rct","tldr":"Adding injections of an engineered adenovirus to chemotherapy roughly doubled the proportion of head and neck or oesophageal cancers that shrank, but the trial reported no survival figures.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"paper-stojdl-vsv-interferon-defect-natmed-2000","kind":"paper","name":"Stojdl 2000: cancer cells that stopped answering interferon cannot stop a virus either","route":"/key-papers/paper-stojdl-vsv-interferon-defect-natmed-2000/","year":2000,"journal":"Nature Medicine","paperType":"basic","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.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"paper-coffey-reovirus-ras-science-1998","kind":"paper","name":"Coffey 1998: reovirus grows in cells with an activated Ras pathway, which describes a great many cancers","route":"/key-papers/paper-coffey-reovirus-ras-science-1998/","year":1998,"journal":"Science","paperType":"basic","tldr":"A common gut virus that does almost nothing in healthy adults turned out to need a switched-on growth pathway to replicate, and that switch is stuck on in a large share of human cancers.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"paper-bischoff-onyx-015-science-1996","kind":"paper","name":"Bischoff 1996: the adenovirus that was said to replicate only where p53 was lost","route":"/key-papers/paper-bischoff-onyx-015-science-1996/","year":1996,"journal":"Science","paperType":"basic","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.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"paper-martuza-engineered-hsv-glioma-science-1991","kind":"paper","name":"Martuza 1991: the first genetically engineered virus built to treat a cancer","route":"/key-papers/paper-martuza-engineered-hsv-glioma-science-1991/","year":1991,"journal":"Science","paperType":"basic","tldr":"A herpes virus was deliberately crippled so that it could only multiply in dividing cells, injected into human brain tumours growing in mice, and it made the mice live longer.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]}],"eras":[{"roadmap":{"id":"immunotherapy-roadmap","kind":"roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-roadmap/"},"era":"2024-2027","title":"Engineered immunity arrives","status":"emerging","step":4,"route":"/roadmaps/immunotherapy-roadmap/#story-step-3","refs":[{"id":"vusolimogene-oderparepvec","kind":"drug","name":"Vusolimogene oderparepvec","route":"/drugs/vusolimogene-oderparepvec/"}]}],"ideas":[{"id":"idea-bio2-oncolytic-regulated-il12","kind":"idea","name":"Oncolytic viruses that make interleukin-12 only inside the tumour","route":"/ideas/idea-bio2-oncolytic-regulated-il12/","maturity":"early-clinical","tldr":"Interleukin-12 is an immune-stimulating cytokine that caused severe toxicity when injected into the bloodstream in the 1990s and was abandoned. An oncolytic herpes or adenovirus carrying the interleukin-12 gene under a drug-inducible promoter makes it only inside the tumour, keeping exposure local; trials include recurrent glioblastoma.","via":[{"id":"cretostimogene","kind":"drug","name":"Cretostimogene grenadenorepvec","route":"/drugs/cretostimogene/"},{"id":"talimogene-laherparepvec","kind":"drug","name":"Talimogene laherparepvec","route":"/drugs/talimogene-laherparepvec/"},{"id":"vusolimogene-oderparepvec","kind":"drug","name":"Vusolimogene oderparepvec","route":"/drugs/vusolimogene-oderparepvec/"},{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"idea-bio2-intranasal-delivery","kind":"idea","name":"Deliver drugs and cells to the brain through the nose","route":"/ideas/idea-bio2-intranasal-delivery/","maturity":"preclinical-evidence","tldr":"The nerves at the top of the nose lead directly into the brain, bypassing the barrier. Nasal delivery of drugs, and even immune cells, has worked in animals.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]},{"id":"idea-moon-cold-to-hot-programme","kind":"idea","name":"Make every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours","route":"/ideas/idea-moon-cold-to-hot-programme/","maturity":"preclinical-evidence","tldr":"Immunotherapy works in tumours that immune cells can enter and ignores those that shut them out. Systematically test ways to open up the shut-out tumours, measured with spatial maps.","via":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}]}],"manufacturing":{"sites":[{"id":"kite-frederick","name":"Kite Frederick","operator":"Kite (Gilead)","operatorRoute":"/companies/gilead/","ownership":"in-house","city":"Frederick, Maryland","country":"US","capabilities":["cell-therapy","viral-vector"],"capabilityLabels":["Cell therapy","Viral vector"],"drugs":[{"id":"axicabtagene-ciloleucel","kind":"drug","name":"Axicabtagene ciloleucel","route":"/drugs/axicabtagene-ciloleucel/"}],"source":{"label":"Kite manufacturing","url":"https://www.kitepharma.com/"}},{"id":"miltenyi-bergisch-gladbach","name":"Miltenyi Biotec","operator":"Miltenyi Biotec","operatorRoute":"/companies/miltenyi-biotec/","ownership":"cdmo","city":"Bergisch Gladbach","country":"DE","capabilities":["cell-therapy","viral-vector"],"capabilityLabels":["Cell therapy","Viral vector"],"drugs":[],"source":{"label":"Miltenyi Biotec","url":"https://www.miltenyibiotec.com/"}},{"id":"oxford-biomedica-oxford","name":"Oxford Biomedica Oxbox","operator":"Oxford Biomedica","operatorRoute":"/companies/oxford-biomedica/","ownership":"cdmo","city":"Oxford","country":"GB","capabilities":["viral-vector"],"capabilityLabels":["Viral vector"],"drugs":[],"source":{"label":"Oxford Biomedica","url":"https://www.oxb.com/"}}],"capabilities":["Viral vector"],"chain":{"id":"cell-therapy","name":"Cell therapy","summary":"Apheresis, vector, closed manufacturing, cryopreservation and chain of identity, release testing, point of care and allogeneic banks.","route":"/manufacturing/#chain-cell-therapy","technologies":[{"id":"apheresis-starting-material","kind":"technology","name":"Apheresis and starting-material collection","route":"/technologies/apheresis-starting-material/"},{"id":"viral-vector-manufacturing","kind":"technology","name":"Viral vector manufacturing (lentiviral, retroviral, AAV)","route":"/technologies/viral-vector-manufacturing/"},{"id":"car-t-manufacturing-process","kind":"technology","name":"Autologous CAR-T manufacturing, batch by batch","route":"/technologies/car-t-manufacturing-process/"},{"id":"closed-automated-cell-manufacturing","kind":"technology","name":"Closed automated cell-therapy manufacturing","route":"/technologies/closed-automated-cell-manufacturing/"},{"id":"cell-therapy-cold-chain","kind":"technology","name":"Cryopreservation and cell-therapy cold chain","route":"/technologies/cell-therapy-cold-chain/"},{"id":"cell-therapy-orchestration-software","kind":"technology","name":"Cell-therapy orchestration and chain-of-identity software","route":"/technologies/cell-therapy-orchestration-software/"},{"id":"cell-therapy-release-testing","kind":"technology","name":"Cell-therapy release and potency testing","route":"/technologies/cell-therapy-release-testing/"},{"id":"point-of-care-cell-manufacturing","kind":"technology","name":"Point-of-care and decentralised cell manufacturing","route":"/technologies/point-of-care-cell-manufacturing/"},{"id":"allogeneic-cell-banks","kind":"technology","name":"Allogeneic cell banks: one donor, hundreds of doses","route":"/technologies/allogeneic-cell-banks/"}],"companies":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"},{"id":"gilead","kind":"company","name":"Gilead Sciences (incl. Kite)","route":"/companies/gilead/"},{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"},{"id":"legend-biotech","kind":"company","name":"Legend Biotech","route":"/companies/legend-biotech/"},{"id":"autolus","kind":"company","name":"Autolus Therapeutics","route":"/companies/autolus/"},{"id":"oxford-biomedica","kind":"company","name":"OXB (Oxford Biomedica)","route":"/companies/oxford-biomedica/"},{"id":"miltenyi-biotec","kind":"company","name":"Miltenyi Biotec","route":"/companies/miltenyi-biotec/"},{"id":"cytiva","kind":"company","name":"Cytiva (Danaher)","route":"/companies/cytiva/"},{"id":"lonza","kind":"company","name":"Lonza","route":"/companies/lonza/"},{"id":"cellares","kind":"company","name":"Cellares","route":"/companies/cellares/"},{"id":"cryoport","kind":"company","name":"Cryoport","route":"/companies/cryoport/"},{"id":"terumo-bct","kind":"company","name":"Terumo Blood and Cell Technologies","route":"/companies/terumo-bct/"},{"id":"cellectis","kind":"company","name":"Cellectis","route":"/companies/cellectis/"},{"id":"allogene","kind":"company","name":"Allogene Therapeutics","route":"/companies/allogene/"},{"id":"immunoact","kind":"company","name":"ImmunoACT","route":"/companies/immunoact/"}],"products":[{"id":"tisagenlecleucel","kind":"drug","name":"Tisagenlecleucel","route":"/drugs/tisagenlecleucel/"},{"id":"axicabtagene-ciloleucel","kind":"drug","name":"Axicabtagene ciloleucel","route":"/drugs/axicabtagene-ciloleucel/"},{"id":"lisocabtagene-maraleucel","kind":"drug","name":"Lisocabtagene maraleucel","route":"/drugs/lisocabtagene-maraleucel/"},{"id":"idecabtagene-vicleucel","kind":"drug","name":"Idecabtagene vicleucel","route":"/drugs/idecabtagene-vicleucel/"},{"id":"ciltacabtagene-autoleucel","kind":"drug","name":"Ciltacabtagene autoleucel","route":"/drugs/ciltacabtagene-autoleucel/"},{"id":"obecabtagene-autoleucel","kind":"drug","name":"Obecabtagene autoleucel","route":"/drugs/obecabtagene-autoleucel/"},{"id":"lifileucel","kind":"drug","name":"Lifileucel","route":"/drugs/lifileucel/"}]},"technologies":[]},"drugs":[{"id":"cretostimogene","kind":"drug","name":"Cretostimogene grenadenorepvec","route":"/drugs/cretostimogene/"},{"id":"h101-oncolytic-adenovirus","kind":"drug","name":"H101 oncolytic adenovirus","route":"/drugs/h101-oncolytic-adenovirus/"},{"id":"olvimulogene-nanivacirepvec","kind":"drug","name":"Olvimulogene nanivacirepvec","route":"/drugs/olvimulogene-nanivacirepvec/"},{"id":"t3011","kind":"drug","name":"T3011","route":"/drugs/t3011/"},{"id":"talimogene-laherparepvec","kind":"drug","name":"Talimogene laherparepvec","route":"/drugs/talimogene-laherparepvec/"},{"id":"theo-260","kind":"drug","name":"THEO-260","route":"/drugs/theo-260/"},{"id":"tilt-123","kind":"drug","name":"TILT-123","route":"/drugs/tilt-123/"},{"id":"vusolimogene-oderparepvec","kind":"drug","name":"Vusolimogene oderparepvec","route":"/drugs/vusolimogene-oderparepvec/"}],"note":"Every section is read from existing corpus records and names them (from, via, exemplars, refs); a section with nothing behind it is empty. Medicines of a format are the open drug engine's (/pipeline/engine/); technologies are listed in src/lib/modular-formats.ts. CC BY-NC 4.0, attribute Data from OnCo (onco.cc). Not medical advice."}