{"entity":{"id":"idea-bio2-in-situ-vaccination-solid","kind":"idea","name":"Turn one tumour into a vaccine to treat all the others","aka":[],"tldr":"Injecting immune-activating agents into a single tumour, plus a small dose of radiation, can teach the immune system to attack tumours elsewhere in the body.","summary":"The in situ vaccine combination of Flt3L to recruit dendritic cells, low-dose radiotherapy to release antigen, and a TLR3 agonist to mature the dendritic cells produced systemic regressions in indolent lymphoma in a phase 1/2 at Mount Sinai. The approach needs no antigen identification and no manufacturing, and has never been properly tested in solid tumours where antigen release by radiotherapy is well characterised.","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":["dlbcl","head-and-neck","sarcoma"],"sections":[],"technologies":["sting-agonist","sbrt","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":["mount-sinai"],"pathways":[],"terms":["abscopal-effect","immunogenic-cell-death","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Intratumoural Flt3L plus low-dose radiotherapy plus a TLR3 agonist induces abscopal responses in at least 15% of patients with checkpoint-refractory solid tumours, with expansion of shared T-cell clones between injected and non-injected lesions.","rationale":"Antigen supply and dendritic cell availability are the two rate-limiting steps for priming in cold tumours, and this regimen supplies both locally at low systemic cost. Clonal sharing between lesions is a hard mechanistic endpoint that does not depend on tumour shrinkage.","test":"A multi-cohort phase 2 in checkpoint-refractory solid tumours with paired injected and distant lesion biopsies and T-cell receptor sequencing as the primary mechanistic endpoint.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},"route":"/ideas/idea-bio2-in-situ-vaccination-solid/","neighbours":{"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"},{"id":"sting-agonist","kind":"technology","name":"STING & innate immune agonists","route":"/technologies/sting-agonist/"}],"institution":[{"id":"mount-sinai","kind":"institution","name":"The Mount Sinai Hospital / Tisch Cancer Institute","route":"/institutions/mount-sinai/"}],"term":[{"id":"abscopal-effect","kind":"term","name":"Abscopal effect","route":"/terms/abscopal-effect/"},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"immunogenic-cell-death","kind":"term","name":"Immunogenic cell death","route":"/terms/immunogenic-cell-death/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"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/"}]}}