# Bispecific antibodies that engage macrophages instead of T cells

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

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed test: 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
- Actor: industry

## 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

- technologies: [Bispecific antibodies](https://onco.cc/technologies/bispecific-antibody/), [CAR-NK & CAR-macrophage](https://onco.cc/technologies/car-nk-macrophage/)
- targets: [CD47](https://onco.cc/targets/cd47/), [HER2](https://onco.cc/targets/her2/), [TROP2](https://onco.cc/targets/trop2/)
- drugs: [Magrolimab](https://onco.cc/drugs/magrolimab/)
- terms: [Fc engineering / effector function](https://onco.cc/terms/fc-effector/), [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/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- 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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