ArticleJournal for immunotherapy of cancer2015
Inhibition of the angiopoietin/Tie2 axis induces immunogenic modulation, which sensitizes human tumor cells to immune attack.
Article in Journal for immunotherapy of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Synergistic anticancer effects of Chrysin and trastuzumab in HER2-Positive breast cancer cells.Scientific reports · 2025Article
- Redlining-associated methylation in breast tumors: the impact of contemporary structural racism on the tumor epigenome.Frontiers in oncology · 2023Article
- Immune-related geneTranslational cancer research · 2021Article
- The Cancer Cell Dissemination Machinery as an Immunosuppressive Niche: A New Obstacle Towards the Era of Cancer Immunotherapy.Frontiers in immunology · 2021Review
- From Immunogenic Cell Death to Immunogenic Modulation: Select Chemotherapy Regimens Induce a Spectrum of Immune-Enhancing Activities in the Tumor Microenvironment.Frontiers in oncology · 2021Review
- Natural Born Killers: NK Cells in Cancer Therapy.Cancers · 2020Review
- Immunometabolic Network Interactions of the Kynurenine Pathway in Cutaneous Malignant Melanoma.Frontiers in oncology · 2020Article
- Dual Inhibition of Angiopoietin-TIE2 and MET Alters the Tumor Microenvironment and Prolongs Survival in a Metastatic Model of Renal Cell Carcinoma.Molecular cancer therapeutics · 2020Article
- Targeting Receptor Kinases in Colorectal Cancer.Cancers · 2019Review
- Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa.Nature reviews. Clinical oncology · 2018Review
- Pediatric Phase I Trial and Pharmacokinetic Study of Trebananib in Relapsed Solid Tumors, Including Primary Tumors of the Central Nervous System ADVL1115: A Children's Oncology Group Phase I Consortium Report.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Ang-2/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The Role of the Tumor Vasculature in the Host Immune Response: Implications for Therapeutic Strategies Targeting the Tumor Microenvironment.Frontiers in immunology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe angiopoietin/Tie2 pathway is an attractive target for cancer therapy due to its well-known role in regulating angiogenesis. Trebananib, a recombinant peptide-Fc fusion protein, or peptibody, that binds to angiopoietin-1 (Ang1) and Ang2 to block their interaction with the Tie2 receptor, is under active clinical investigation. We investigated whether suppressing the angiopoietin/Tie2 pathway, using the preclinical version of Trebananib (mL4-3 and L1-7(N)), could increase the sensitivity of human tumor cells to immune-mediated lysis through immunogenic modulation, which would make Trebananib a promising candidate for combination with immunotherapy.
methodsWe assessed human carcinoma cells for expression and activation of Ang1 and Ang2 and their receptor tyrosine kinase Tie2. In vitro, we exposed tumor cell lines expressing Tie2 to the peptibodies mL4-3 and L1-7(N), which inhibit the binding of Ang1 and Ang2 to Tie2, and assessed the cells for changes in viability, proliferation, surface phenotype, and sensitivity to attack by antigen-specific cytotoxic T lymphocytes (CTLs).
resultsSuppression of the angiopoietin/Tie2 pathway using mL4-3 and L1-7(N) had no effect on the proliferation or viability of tumor cells. However, these inhibitors markedly altered tumor cell phenotype, rendering tumor cells significantly more sensitive to antigen-specific CTL killing. ICAM-1 was shown to be mechanistically involved in these inhibitors' ability to sensitize tumor cells to immune-mediated attack by functional blocking studies.
conclusionOur findings provide a rationale for the combination of agents targeting the angiopoietin/Tie2 pathway with cancer immunotherapies.
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