ArticleProceedings of the National Academy of Sciences of the United States of America2018
Anti-CTLA-4 therapy requires an Fc domain for efficacy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Neoadjuvant PD-1/PD-L1 combined with CTLA-4 inhibitors for solid malignancies: a systematic review and meta-analysis.World journal of surgical oncology · 2023Pooled it
- Depletion of Effector Regulatory T Cells Associates with Major Response to Induction Dual Immune Checkpoint Blockade.Cancer discovery · 2025Trial
- Review
- Regulatory T Cells in Hepatocellular Carcinoma: Spatial Niches, Biomarkers, and Clinical Implications.International journal of molecular sciences · 2026Review
- Rethinking biomarker strategy in gastric cancer immunotherapy: from tumor to host.Frontiers in immunology · 2026Review
- Nanobody-based bispecific antibody engagers targeting CTLA-4 or PD-L1 for cancer immunotherapy.Nature biomedical engineering · 2026Article
- Prostaglandin EProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Unveiling the molecular and immunological drivers of antibody-drug conjugates in cancer treatment.Nature reviews. Cancer · 2025Review
- ImmunoPET imaging of c-Met using a nanobody-based tracer [European journal of nuclear medicine and molecular imaging · 2025Article
- Review
- Fc-optimized anti-CTLA-4 antibodies increase tumor-associated high endothelial venules and sensitize refractory tumors to PD-1 blockade.Cell reports. Medicine · 2025Article
- CTLA-4-two pathways to anti-tumour immunity?Immunotherapy advances · 2025Review
- Preclinical development of a novel CCR8/CTLA-4 bispecific antibody for cancer treatment by disrupting CTLA-4 signaling on CD8 T cells and specifically depleting tumor-resident Tregs.Cancer immunology, immunotherapy : CII · 2024Article
- Characterization of a novel anti-PVRIG antibody with Fc-competent function that exerts strong antitumor effects via NK activation in preclinical models.Cancer immunology, immunotherapy : CII · 2024Article
- FcγRIIB Is an Immune Checkpoint Limiting the Activity of Treg-Targeting Antibodies in the Tumor Microenvironment.Cancer immunology research · 2024Article
- Evaluation of regulatory T-cells in cancer immunotherapy: therapeutic relevance of immune checkpoint inhibition.Medical oncology (Northwood, London, England) · 2024Review
- Anti-CTLA-4 nanobody as a promising approach in cancer immunotherapy.Cell death & disease · 2024Review
- Machine learning based anoikis signature predicts personalized treatment strategy of breast cancer.Frontiers in immunology · 2024Article
- Advancements in nuclear imaging using radiolabeled nanobody tracers to support cancer immunotherapy.Immunotherapy advances · 2024Review
- Fusing a Novel Anti-CTLA-4 Nanobody to the IgG1 Fc Region Strengthens Its Ability to Induce CD8International journal of nanomedicine · 2024Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Ipilimumab, a monoclonal antibody that recognizes cytotoxic T lymphocyte antigen (CTLA)-4, was the first approved "checkpoint"-blocking anticancer therapy. In mouse tumor models, the response to antibodies against CTLA-4 depends entirely on expression of the Fcγ receptor (FcγR), which may facilitate antibody-dependent cellular phagocytosis, but the contribution of simple CTLA-4 blockade remains unknown. To understand the role of CTLA-4 blockade in the complete absence of Fc-dependent functions, we developed H11, a high-affinity alpaca heavy chain-only antibody fragment (VHH) against CTLA-4. The VHH H11 lacks an Fc portion, binds monovalently to CTLA-4, and inhibits interactions between CTLA-4 and its ligand by occluding the ligand-binding motif on CTLA-4 as shown crystallographically. We used H11 to visualize CTLA-4 expression in vivo using whole-animal immuno-PET, finding that surface-accessible CTLA-4 is largely confined to the tumor microenvironment. Despite this, H11-mediated CTLA-4 blockade has minimal effects on antitumor responses. Installation of the murine IgG2a constant region on H11 dramatically enhances its antitumor response. Coadministration of the monovalent H11 VHH blocks the efficacy of a full-sized therapeutic antibody. We were thus able to demonstrate that CTLA-4-binding antibodies require an Fc domain for antitumor effect.
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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.