ArticleScience translational medicine2023
Soluble CTLA-4 mutants ameliorate immune-related adverse events but preserve efficacy of CTLA-4- and PD-1-targeted immunotherapy.
Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 15 citations in OpenAlex.
- The Cardio-Onco-Immune Axis: immunopathological mechanisms in the cardiac microenvironment of checkpoint inhibitor-induced myocarditis.Acta pharmacologica Sinica · 2026Review
- Review
- Understanding immune checkpoint inhibitors-related myocarditis: Mechanisms and targeted therapeutic pathways.Theranostics · 2026Review
- Soluble CTLA-4 as a context-dependent immune checkpoint: biology, biomarker potential, and therapeutic implications.Frontiers in immunology · 2026Review
- M5542, a bifunctional fusion protein targeting CD80, CD86, and OX40L that modulates excessive T-cell activity: a preclinical proof-of-concept study.Frontiers in immunology · 2026Article
- Single-cell transcriptomic insights into the immune heterogeneity of immune checkpoint inhibitors related organ toxicities.Frontiers in immunology · 2026Review
- Radiation therapy causes a STING and MyD88-independent upregulation of CD80 and CD86 in macrophages and monocytes that limits tumor control.Cancer immunology, immunotherapy : CII · 2025Article
- Risk factors and mechanisms of immune checkpoint inhibitor-related pneumonitis.Human vaccines & immunotherapeutics · 2025Review
- Life-threatening immune-related adverse events in the intensive care unit: a narrative review.Intensive care medicine · 2025Review
- Impact of tumor localization on antitumor immunity with conditionally activated CTLA-4 blockade.Journal for immunotherapy of cancer · 2025Article
- Article
- The impact of immune checkpoint inhibition on atherosclerosis in cancer patients.Frontiers in immunology · 2025Review
- Gasdermin-E-mediated pyroptosis drives immune checkpoint inhibitor-associated myocarditis via cGAS-STING activation.Nature communications · 2024Article
- Immune checkpoints in cardiac physiology and pathology: therapeutic targets for heart failure.Nature reviews. Cardiology · 2024Review
- Article
- CTLA-4 antibody-drug conjugate reveals autologous destruction of B-lymphocytes associated with regulatory T cell impairment.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 3 countries.
Funding
Abstract
Immune checkpoint inhibitors (ICIs), such as nivolumab and ipilimumab, not only elicit antitumor responses in a wide range of human cancers but also cause severe immune-related adverse events (irAEs), including death. A largely unmet medical need is to treat irAEs without abrogating the immunotherapeutic effect of ICIs. Although abatacept has been used to treat irAEs, it risks neutralizing the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) monoclonal antibodies administered for cancer therapy, thereby reducing the efficacy of anti-CTLA-4 immunotherapy. To avoid this caveat, we compared wild-type abatacept and mutants of CTLA-4-Ig for their binding to clinically approved anti-CTLA-4 antibodies and for their effect on both irAEs and immunotherapy conferred by anti-CTLA-4 and anti-PD-1 antibodies. Here, we report that whereas abatacept neutralized the therapeutic effect of anti-CTLA-4 antibodies, the mutants that bound to B7-1 and B7-2, but not to clinical anti-CTLA-4 antibodies, including clinically used belatacept, abrogated irAEs without affecting cancer immunotherapy. Our data demonstrate that anti-CTLA-4-induced irAEs can be corrected by provision of soluble CTLA-4 variants and that the clinically available belatacept may emerge as a broadly applicable drug to abrogate irAEs while preserving the therapeutic efficacy of CTLA-4-targeting ICIs.
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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.