OnCo
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

Connected

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Pages like this

not linked directly; found by shared links

technologies

2
Bispecific antibodiesCAR-NK & CAR-macrophage

targets

3
CD47HER2TROP2

drugs

1
WithdrawnMonoclonal antibody (anti-CD47)
Magrolimab

terms

2
Fc engineering / effector functionHot vs cold tumours

bottlenecks

2
Cold tumours and the immunosuppressive microenvironmentToxicity and quality of life are undervalued