{"entity":{"id":"idea-bio2-myeloid-engager-bispecific","kind":"idea","name":"Bispecific antibodies that engage macrophages instead of T cells","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"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)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["bispecific-antibody","car-nk-macrophage"],"targets":["cd47","her2","trop2"],"drugs":["magrolimab"],"companies":[],"institutions":[],"pathways":[],"terms":["fc-effector","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-toxicity-qol"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"medium","horizonYears":7},"route":"/ideas/idea-bio2-myeloid-engager-bispecific/","neighbours":{"technology":[{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"},{"id":"car-nk-macrophage","kind":"technology","name":"CAR-NK & CAR-macrophage","route":"/technologies/car-nk-macrophage/"}],"target":[{"id":"cd47","kind":"target","name":"CD47","route":"/targets/cd47/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"trop2","kind":"target","name":"TROP2","route":"/targets/trop2/"}],"drug":[{"id":"magrolimab","kind":"drug","name":"Magrolimab","route":"/drugs/magrolimab/"}],"term":[{"id":"fc-effector","kind":"term","name":"Fc engineering / effector function","route":"/terms/fc-effector/"},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"paper":[{"id":"paper-haslam-jama-netw-open","kind":"paper","name":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","route":"/key-papers/paper-haslam-jama-netw-open/"}]}}