ArticlemAbs
Improved therapeutic index of an acidic pH-selective antibody.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- The evolution of display technologies for antibody drug discovery.Trends in biotechnology · 2026Review
- Review
- Pathophysiological and Etiological Corroborations for the Mechanistic Design of Intranasal Therapies in Glioblastoma Multiforme.Current pharmaceutical design · 2026Review
- Conditionally Activatable Antibody Platforms: Mechanisms, Modalities, and Clinical Translation Potential.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Article
- Strategies to Screen and Evaluate Brain Targeting Antibodies Using an iPSC-Derived Blood-Brain Barrier Model.Antibodies (Basel, Switzerland) · 2025Article
- Article
- Generation Using Phage-Display of pH-Dependent Antibodies Against the Tumor-Associated Antigen AXL.Antibodies (Basel, Switzerland) · 2025Article
- Computational design of pH-sensitive binders.bioRxiv : the preprint server for biology · 2025Article
- Negative Immune Checkpoint Inhibitors.Pharmaceutics · 2025Review
- Targeting Aging Hallmarks with Monoclonal Antibodies: A New Era in Cancer Immunotherapy and Geriatric Medicine.International journal of molecular sciences · 2025Review
- Tumor-Specific Antigen Delivery for T-cell Therapy via a pH-Sensitive Peptide Conjugate.Molecular cancer therapeutics · 2025Article
- Enhanced and Efficient Predictions of Dynamic Ionization through Constant-pH Adiabatic Free Energy Dynamics.Journal of chemical theory and computation · 2024Article
- Conditionally Active, pH-Sensitive Immunoregulatory Antibodies Targeting VISTA and CTLA-4 Lead an Emerging Class of Cancer Therapeutics.Antibodies (Basel, Switzerland) · 2023Review
- Comparative Performance of High-Throughput Methods for Protein pJournal of chemical information and modeling · 2023Article
- Metabolic adaptations of cancer in extreme tumor microenvironments.Cancer science · 2023Review
- Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials.Signal transduction and targeted therapy · 2022Review
- Tumor acidity: From hallmark of cancer to target of treatment.Frontiers in oncology · 2022Review
- Article
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 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although therapeutically efficacious, ipilimumab can exhibit dose-limiting toxicity that prevents maximal efficacious clinical outcomes and can lead to discontinuation of treatment. We hypothesized that an acidic pH-selective ipilimumab (pH Ipi), which preferentially and reversibly targets the acidic tumor microenvironment over the neutral periphery, may have a more favorable therapeutic index. While ipilimumab has pH-independent CTLA-4 affinity, pH Ipi variants have been engineered to have up to 50-fold enhanced affinity to CTLA-4 at pH 6.0 compared to pH 7.4. In hCTLA-4 knock-in mice, these variants have maintained anti-tumor activity and reduced peripheral activation, a surrogate marker for toxicity. pH-sensitive therapeutic antibodies may be a differentiating paradigm and a novel modality for enhanced tumor targeting and improved safety profiles.
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What Socratic holds
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 Socratic graph.