{"entity":{"id":"idea-bio2-oncolytic-regulated-il12","kind":"idea","name":"Oncolytic viruses that make interleukin-12 only inside the tumour","aka":[],"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.","summary":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["glioblastoma","melanoma","urothelial"],"sections":[],"technologies":["oncolytic-virus","cytokine-therapy","checkpoint-inhibitor"],"targets":[],"drugs":["talimogene-laherparepvec","vusolimogene-oderparepvec","cretostimogene","nadofaragene-firadenovec"],"companies":["replimune","cg-oncology"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["kevin-harrington"],"bottlenecks":["b-tme-immunosuppression","b-brain-delivery"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A regulated intratumoural interleukin-12 payload achieves tumour-to-plasma cytokine ratios above 100 and produces T-cell infiltration in previously cold lesions, without dose-limiting systemic toxicity.","rationale":"The failure of interleukin-12 was pharmacokinetic, not immunological, and local delivery is exactly the right fix. Oncolytic products are already approved in melanoma and bladder cancer, so the manufacturing and regulatory route exists.","test":"Dose-escalation with paired biopsies and matched plasma cytokine measurement, reporting tumour-to-plasma ratio and change in CD8 density as the primary endpoints, before efficacy expansion.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":7},"route":"/ideas/idea-bio2-oncolytic-regulated-il12/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"technology":[{"id":"cytokine-therapy","kind":"technology","name":"Cytokines & engineered cytokines","route":"/technologies/cytokine-therapy/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}],"drug":[{"id":"cretostimogene","kind":"drug","name":"Cretostimogene grenadenorepvec","route":"/drugs/cretostimogene/"},{"id":"nadofaragene-firadenovec","kind":"drug","name":"Nadofaragene firadenovec","route":"/drugs/nadofaragene-firadenovec/"},{"id":"talimogene-laherparepvec","kind":"drug","name":"Talimogene laherparepvec","route":"/drugs/talimogene-laherparepvec/"},{"id":"vusolimogene-oderparepvec","kind":"drug","name":"Vusolimogene oderparepvec","route":"/drugs/vusolimogene-oderparepvec/"}],"company":[{"id":"cg-oncology","kind":"company","name":"CG Oncology","route":"/companies/cg-oncology/"},{"id":"replimune","kind":"company","name":"Replimune","route":"/companies/replimune/"}],"person":[{"id":"kevin-harrington","kind":"person","name":"Kevin Harrington","route":"/people/kevin-harrington/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"}],"paper":[{"id":"paper-haslam-jama-netw-open","kind":"paper","name":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","route":"/key-papers/paper-haslam-jama-netw-open/"}]}}