# Turn one tumour into a vaccine to treat all the others

Source: https://onco.cc/ideas/idea-bio2-in-situ-vaccination-solid/  
OnCo record `idea-bio2-in-situ-vaccination-solid` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- 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): https://doi.org/10.1001/jamanetworkopen.2019.2535

## Connected records

- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/), [STING & innate immune agonists](https://onco.cc/technologies/sting-agonist/)
- institutions: [The Mount Sinai Hospital / Tisch Cancer Institute](https://onco.cc/institutions/mount-sinai/)
- terms: [Abscopal effect](https://onco.cc/terms/abscopal-effect/), [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Immunogenic cell death](https://onco.cc/terms/immunogenic-cell-death/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/)
- key papers: [Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs](https://onco.cc/key-papers/paper-haslam-jama-netw-open/)

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