OnCo
ideasIdea

Block the complement signal that recruits tumour-protecting cells

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.

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.

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.
What would test it
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
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
7
Bottlenecks it attacks

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