ideasIdea
Bispecific antibodies that engage macrophages instead of T cells
Drugs that grab T cells and drag them onto tumours work well in blood cancers. The same trick aimed at tumour-eating cells might work where T cells are absent.
T-cell engagers require T cells to be present and functional, which fails in T-cell-poor tumours. Myeloid engagers pairing a tumour antigen with CD47 blockade, SIRP-alpha, CD40 or Fc-gamma receptor agonism localise phagocytic activation to tumour tissue, potentially avoiding the anaemia that limited systemic anti-CD47 antibodies.
Hypothesis
A tumour-antigen-anchored myeloid engager produces tumour regression in T-cell-poor models and, in humans, increases phagocytic marker expression in tumour biopsies without the haemolytic anaemia seen with systemic CD47 blockade.
Rationale
Systemic CD47 blockade failed on toxicity and on-target effects in red cells, a classic index problem solved by tumour anchoring. Macrophages are abundant in exactly the tumours where T cells are scarce, so the effector cell is already in place.
What would test it
Preclinical comparison of anchored versus systemic CD47 blockade for haematological toxicity and efficacy, then a phase 1 with biopsy-based phagocytosis pharmacodynamics.
Maturity
preclinical evidence
Who has to act
industry
Cost to try
Medium ($1M to $50M)
Years to first evidence
7
Bottlenecks it attacks
- Cold tumours and the immunosuppressive microenvironment · Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.
- Toxicity and quality of life are undervalued · Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated.