ArticleCancer immunology research2024
Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor Effects.
Article in Cancer immunology research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Bone targeted microenvironment actuated engineered exosomes for precision therapy of IBD associated bone loss.Bioactive materials · 2026Article
- Anisodus tanguticus in Cancer Research: A Review of Traditional Use, Phytochemistry, Extraction Methods, and Preclinical Antitumor Evidence.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026Review
- Anti-PD1-IL18 immunoconjugate promotes effector T cell-mediated antitumor immunity.Journal for immunotherapy of cancer · 2026Article
- Establishment and validation of a prognostic model for pancreatic cancer utilizing genes of tumor-associated neutrophils.Discover oncology · 2026Article
- AI platform for CRISPR functional mapping and function-based drug design.bioRxiv : the preprint server for biology · 2026Article
- Article
- Analysis of the NLRP3 inflammasome components expression in triple-negative breast cancer patients with and without BRCA1 mutations.Scientific reports · 2026Article
- The Roles of Interleukin-18 in Inflammation and Autoimmune Disease.Clinical reviews in allergy & immunology · 2026Review
- Host Prior Exposure Augments Gene Expression Heterogeneity of Both Host and Pathogen During In Vivo Infection.Molecular ecology · 2026Article
- Liver metastases dampen IL18-driven γδ T cell activity and immunotherapy responsiveness in colorectal cancer.Cell reports. Medicine · 2026Article
- IL-18-Mediated Tumor Immune Evasion.Current issues in molecular biology · 2026Review
- Inflammasomes and pyroptosis in cancer: mechanisms and therapeutic advances.Journal of hematology & oncology · 2025Review
- Innate and adaptive immune features associated with immune-related adverse events.Journal for immunotherapy of cancer · 2025Article
- Host prior exposure augments heterogeneity in gene expression in both host and pathogen duringbioRxiv : the preprint server for biology · 2025Article
- The causal relationship between inflammatory cytokines and lung cancer: a two-sample bidirectional mendelian randomization study.Discover oncology · 2025Article
- Weal and woe of interleukin-18 in the T cell therapy of cancer.Journal for immunotherapy of cancer · 2025Review
- Targeting highly attenuated IL-18 to PD-1 for enhanced anti-tumor activity.Frontiers in immunology · 2025Article
- Development of anti-murine IL-18 binding protein antibodies to stimulate IL-18 bioactivity.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Circulating innate lymphoid cells and IL-18 as potential immune biomarkers in thymic tumors.Frontiers in immunology · 2025Article
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31 authors.
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Abstract
Recombinant cytokines have limited anticancer efficacy mostly due to a narrow therapeutic window and systemic adverse effects. IL18 is an inflammasome-induced proinflammatory cytokine, which enhances T- and NK-cell activity and stimulates IFNγ production. The activity of IL18 is naturally blocked by a high-affinity endogenous binding protein (IL18BP). IL18BP is induced in the tumor microenvironment (TME) in response to IFNγ upregulation in a negative feedback mechanism. In this study, we found that IL18 is upregulated in the TME compared with the periphery across multiple human tumors and most of it is bound to IL18BP. Bound IL18 levels were largely above the amount required for T-cell activation in vitro, implying that releasing IL18 in the TME could lead to potent T-cell activation. To restore the activity of endogenous IL18, we generated COM503, a high-affinity anti-IL18BP that blocks the IL18BP:IL18 interaction and displaces precomplexed IL18, thereby enhancing T- and NK-cell activation. In vivo, administration of a surrogate anti-IL18BP, either alone or in combination with anti-PD-L1, resulted in significant tumor growth inhibition and increased survival across multiple mouse tumor models. Moreover, the anti-IL18BP induced pronounced TME-localized immune modulation including an increase in polyfunctional nonexhausted T- and NK-cell numbers and activation. In contrast, no increase in inflammatory cytokines and lymphocyte numbers or activation state was observed in serum and spleen. Taken together, blocking IL18BP using an Ab is a promising approach to harness cytokine biology for the treatment of cancer.
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