# Block the complement signal that recruits tumour-protecting cells

Source: https://onco.cc/ideas/idea-bio2-complement-c5ar-blockade/  
OnCo record `idea-bio2-complement-c5ar-blockade` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An old part of the immune system called complement can be hijacked by tumours to summon protective cells. Drugs that block it already exist for other diseases.

## Summary

C5a acting through C5aR1 recruits and polarises suppressive myeloid cells in lung, cervical and pancreatic tumour models, and complement inhibitors are approved for rare haematological and kidney diseases, giving established safety data. Combination with checkpoint blockade showed additive effects in mouse models, and small early-phase trials of anti-C5aR1 with checkpoint inhibitors have begun.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: C5aR1 blockade reduces suppressive myeloid infiltration in human tumours and restores checkpoint response in tumours with high complement activation signatures.
- Rationale: Complement is an unusual immunotherapy target because clinical-grade inhibitors already exist for other indications, so repositioning is fast. Complement activation signatures are measurable in tissue and plasma, allowing patient selection from the outset.
- Proposed test: Signature-selected phase 1b with paired biopsies measuring myeloid infiltration and complement activation, plus a plasma pharmacodynamic assay to confirm target coverage.
- Maturity: preclinical-evidence
- 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: [Cervical cancer](https://onco.cc/cancers/cervical/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/)
- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/), [No incentive to repurpose cheap drugs](https://onco.cc/bottlenecks/b-generic-repurposing/)
- 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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