ArticleProceedings of the National Academy of Sciences of the United States of America2017
Structural basis for cancer immunotherapy by the first-in-class checkpoint inhibitor ipilimumab.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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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
93 citing papers in PubMed, 155 citations in OpenAlex.
- Immune Checkpoint Inhibitor-Associated Cardiovascular Toxicity: Mechanisms, Clinical Manifestations, and Clinical Impact.Cardiovascular toxicology · 2026Review
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- Expression of FoxP3 in oral squamous cell carcinoma and its biological significance.Discover oncology · 2025Article
- Novel Chimeric CTLA-4 B-cell Epitope Peptide Vaccines Demonstrate Effective Antitumor Immunity with/without PD1/PDL1 Blockade in Multiple Syngeneic Murine Models of Breast and Colorectal Cancers.Molecular cancer therapeutics · 2025Article
- Emerging new immune checkpoint inhibitors in solid tumor immunotherapy.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- TIGIT in cancer: from mechanism of action to promising immunotherapeutic strategies.Cell death & disease · 2025Review
- Phenotypic and targeted drug discovery in immune therapeutics: challenges, opportunities, and future directions.RSC advances · 2025Review
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- Innovative Immunotherapy and Its Transformative Impact on Gastric Adenocarcinoma: A Comprehensive Review of the Disease's Origins, Epidemiology, Classification, Diagnosis, and Treatment Options.ACS pharmacology & translational science · 2025Review
- Negative Immune Checkpoint Inhibitors.Pharmaceutics · 2025Review
- Disulfidptosis-related LncRNAs forecast the prognosis of acute myeloid leukemia.Scientific reports · 2025Article
- Immune Checkpoint Molecules: A Review on Pathways and Immunotherapy Implications.Immunity, inflammation and disease · 2025Review
- Review
- Clinical and experimental treatment of advanced melanoma with a focus on immunotherapy.Clinical and experimental immunology · 2025Review
- Beyond monotherapy: multimodal strategies integrating immune checkpoint inhibitors in lymphoma management.Frontiers in immunology · 2025Review
- Botensilimab, an Fc-Enhanced Anti-CTLA-4 Antibody, Is Effective against Tumors Poorly Responsive to Conventional Immunotherapy.Cancer discovery · 2024Article
- Real‑world evidence of advanced non‑small cell lung carcinoma treated with an immune checkpoint inhibitor plus chemotherapy.Oncology letters · 2024Article
- Soluble CTLA-4 attenuates T cell activation and modulates anti-tumor immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Expanding the molecular and phenotypic spectrum of CTLA-4 insufficiency.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2024Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Rational modulation of the immune response with biologics represents one of the most promising and active areas for the realization of new therapeutic strategies. In particular, the use of function blocking monoclonal antibodies targeting checkpoint inhibitors such as CTLA-4 and PD-1 have proven to be highly effective for the systemic activation of the human immune system to treat a wide range of cancers. Ipilimumab is a fully human antibody targeting CTLA-4 that received FDA approval for the treatment of metastatic melanoma in 2011. Ipilimumab is the first-in-class immunotherapeutic for blockade of CTLA-4 and significantly benefits overall survival of patients with metastatic melanoma. Understanding the chemical and physical determinants recognized by these mAbs provides direct insight into the mechanisms of pathway blockade, the organization of the antigen-antibody complexes at the cell surface, and opportunities to further engineer affinity and selectivity. Here, we report the 3.0 Å resolution X-ray crystal structure of the complex formed by ipilimumab with its human CTLA-4 target. This structure reveals that ipilimumab contacts the front β-sheet of CTLA-4 and intersects with the CTLA-4:Β7 recognition surface, indicating that direct steric overlap between ipilimumab and the B7 ligands is a major mechanistic contributor to ipilimumab function. The crystallographically observed binding interface was confirmed by a comprehensive cell-based binding assay against a library of CTLA-4 mutants and by direct biochemical approaches. This structure also highlights determinants responsible for the selectivity exhibited by ipilimumab toward CTLA-4 relative to the homologous and functionally related CD28.
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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.