# Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity

Source: https://onco.cc/roadmaps/immunotherapy-roadmap/  
OnCo record `immunotherapy-roadmap` (Roadmap). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The immunotherapy roadmap is a 130-year arc from injecting bacteria into tumours to releasing immune brakes, and now to designing the immune response itself with vaccines, engagers, and cells.

## Summary

The immunotherapy roadmap covers a 130-year arc that starts with Coley's toxins, BCG for bladder cancer, interferon and IL-2 and sipuleucel-T, an era of sporadic cures and scepticism. The checkpoint revolution followed with ipilimumab, nivolumab, pembrolizumab and atezolizumab and the Nobel Prize to Allison and Honjo, then immunotherapy moved into earlier lines, combinations, T-cell engagers and TIL. The emerging step is engineered immunity: personalised mRNA vaccines, PD-1 and VEGF bispecifics, ADC plus IO, oncolytic viruses, TCR-T and in vivo CAR, with interception vaccines as the speculative end. The route links checkpoint inhibitors, T-cell engagers, CAR-T, TIL and STING agonists, and the cold-tumour and response-prediction bottlenecks.

## Fields

- Kind: Roadmap
- Last checked: 2026-09-04

## Sources

- Leach, Krummel and Allison: releasing the CTLA-4 brake makes mice reject tumours (Science 1996): https://doi.org/10.1126/science.271.5256.1734
- Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma (New England Journal of Medicine 2010): https://doi.org/10.1056/NEJMoa1003466

## Connected records

- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/), [Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials](https://onco.cc/roadmaps/gallbladder-cancer-roadmap/), [Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/), [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/), [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/), [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- fronts: [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- technologies: [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [Cytokines & engineered cytokines](https://onco.cc/technologies/cytokine-therapy/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Immuno-PET](https://onco.cc/technologies/immuno-pet/), [In vivo CAR-T](https://onco.cc/technologies/in-vivo-car-t/), [Off-the-shelf cancer vaccines](https://onco.cc/technologies/shared-antigen-vaccine/), [Oncolytic viruses](https://onco.cc/technologies/oncolytic-virus/), [Personalised neoantigen (mRNA) vaccines](https://onco.cc/technologies/neoantigen-mrna-vaccine/), [STING & innate immune agonists](https://onco.cc/technologies/sting-agonist/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/), [TIL therapy](https://onco.cc/technologies/til-therapy/)
- drugs: [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Ivonescimab](https://onco.cc/drugs/ivonescimab/), [Lifileucel](https://onco.cc/drugs/lifileucel/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Relatlimab + nivolumab](https://onco.cc/drugs/relatlimab-nivolumab/), [Tarlatamab](https://onco.cc/drugs/tarlatamab/), [Vusolimogene oderparepvec](https://onco.cc/drugs/vusolimogene-oderparepvec/)
- trials: [ASCENT-04 / KEYNOTE-D19](https://onco.cc/trials/ascent-04/), [CheckMate 067](https://onco.cc/trials/checkmate-067/), [INTerpath-001 (V940-001)](https://onco.cc/trials/interpath-001/), [KEYNOTE-522](https://onco.cc/trials/keynote-522/)
- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/)
- cancers: [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Melanoma](https://onco.cc/cancers/melanoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- key papers: [Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC](https://onco.cc/key-papers/paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020/), [RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer](https://onco.cc/key-papers/paper-sethna-rna-neoantigen-vaccine-long-lived-t-cells-nature-2025/)
- ideas: [Select microsatellite stable patients for immunotherapy by a measured immune biomarker, not by how many treatments they have already failed](https://onco.cc/ideas/idea-crc-mss-immunotherapy-by-biomarker-not-by-line/)
- 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/)

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