ArticleJournal for immunotherapy of cancer2019
Bi- and tri-valent T cell engagers deplete tumour-associated macrophages in cancer patient samples.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 73 citations in OpenAlex.
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- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Advancing immunotherapy via multiple immune cells co-engagement.Frontiers in immunology · 2026Review
- CAR T Cell Therapy in Lung Cancer: Overcoming Tumor Microenvironment-Mediated Barriers.International journal of biological sciences · 2026Review
- FOLR2Cell communication and signaling : CCS · 2025Review
- Mechanistic insights into resistance mechanisms to T cell engagers.Frontiers in immunology · 2025Review
- Engaging T cells for cleanup.Frontiers in immunology · 2025Review
- How to Use Macrophages Against Cancer.Cells · 2024Review
- Reprogramming exosomes for immunity-remodeled photodynamic therapy against non-small cell lung cancer.Bioactive materials · 2024Article
- Oncolytic virus and tumor-associated macrophage interactions in cancer immunotherapy.Clinical and experimental medicine · 2024Review
- Revolutionizing cancer treatment: the power of bi- and tri-specific T-cell engagers in oncolytic virotherapy.Frontiers in immunology · 2024Review
- Improving the therapeutic efficacy of oncolytic viruses for cancer: targeting macrophages.Journal of translational medicine · 2023Review
- Recent Advances in Folates and Autoantibodies against Folate Receptors in Early Pregnancy and Miscarriage.Nutrients · 2023Review
- Emerging Immunotherapy Approaches for Treating Prostate Cancer.International journal of molecular sciences · 2023Review
- Bispecific T-Cell Engagers and Chimeric Antigen Receptor T-Cell Therapies in Glioblastoma: An Update.Current oncology (Toronto, Ont.) · 2023Review
- The potential of monoclonal antibodies for colorectal cancer therapy.Medical oncology (Northwood, London, England) · 2023Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundTumour-associated macrophages (TAMs) are often implicated in cancer progression but can also exert anti-tumour activities. Selective eradication of cancer-promoting (M2-like) TAM subsets is a highly sought-after goal. Here, we have devised a novel strategy to achieve selective TAM depletion, involving the use of T cell engagers to direct endogenous T cell cytotoxicity towards specific M2-like TAMs. To avoid "on-target off-tumour" toxicities, we have explored localising expression of the T cell engagers to the tumour with enadenotucirev (EnAd), an oncolytic adenovirus in Phase I/II clinical trials.
methodA panel of bi- and tri-valent T cell engagers (BiTEs/TriTEs) was constructed, recognising CD3ε on T cells and CD206 or folate receptor β (FRβ) on M2-like macrophages. Initial characterisation of BiTE/TriTE activity and specificity was performed with M1- and M2-polarised monocyte-derived macrophages and autologous lymphocytes from healthy human peripheral blood donors. T cell engagers were inserted into the genome of EnAd, and oncolytic activity and BiTE secretion assessed with DLD-1 tumour cells. Clinically-relevant ex vivo models (whole malignant ascites from cancer patients) were employed to assess the efficacies of the free- and virally-encoded T cell engagers.
resultsT cells activated by the CD206- and FRβ-targeting BiTEs/TriTEs preferentially killed M2- over M1-polarised autologous macrophages, with EC
conclusionsThis study is the first to achieve selective depletion of specific M2-like macrophage subsets, opening the possibility of eradicating cancer-supporting TAMs whilst sparing those with anti-tumour potential. Targeted TAM depletion with T cell engager-armed EnAd offers a powerful therapeutic approach combining direct cancer cell cytotoxicity with reversal of immune suppression.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.