ArticleCancer immunology research2021
Conditional PD-1/PD-L1 Probody Therapeutics Induce Comparable Antitumor Immunity but Reduced Systemic Toxicity Compared with Traditional Anti-PD-1/PD-L1 Agents.
Article in Cancer immunology research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- The prognostic value of prognostic nutritional index in advanced cancer receiving PD-1/L1 inhibitors: A meta-analysis.Cancer medicine · 2022Pooled it
- Chemically Masked aPD-L1-Sialidase Conjugate for Tumor-Specific Desialylation and Immunotherapy.Angewandte Chemie (International ed. in English) · 2026Article
- Conditionally Activatable Antibody Platforms: Mechanisms, Modalities, and Clinical Translation Potential.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Phenotypic and targeted drug discovery in immune therapeutics: challenges, opportunities, and future directions.RSC advances · 2025Review
- A masking clamp for conditional activation of therapeutic antibodies.Frontiers in immunology · 2025Article
- Virtual clinical trials via a QSP immuno-oncology model to simulate the response to a conditionally activated PD-L1 targeting antibody in NSCLC.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- A Generic Antibody-Blocking Protein That Enables pH-Switchable Activation of Antibody Activity.ACS chemical biology · 2024Article
- NSCLC: from tumorigenesis, immune checkpoint misuse to current and future targeted therapy.Frontiers in immunology · 2024Review
- Eliciting the antitumor immune response with a conditionally activated PD-L1 targeting antibody analyzed with a quantitative systems pharmacology model.CPT: pharmacometrics & systems pharmacology · 2024Article
- Development of antibody-drug conjugates in cancer: Overview and prospects.Cancer communications (London, England) · 2024Review
- In silico evolution of autoinhibitory domains for a PD-L1 antagonist using deep learning models.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Crosstalk of ferroptosis regulators and tumor immunity in pancreatic adenocarcinoma: novel perspective to mRNA vaccines and personalized immunotherapy.Apoptosis : an international journal on programmed cell death · 2023Article
- Conditionally Active, pH-Sensitive Immunoregulatory Antibodies Targeting VISTA and CTLA-4 Lead an Emerging Class of Cancer Therapeutics.Antibodies (Basel, Switzerland) · 2023Review
- Article
- Strategies for Conditional Regulation of Proteins.JACS Au · 2023Review
- Targeting syndecan-1: new opportunities in cancer therapy.American journal of physiology. Cell physiology · 2022Review
- Exploiting protease activation for therapy.Drug discovery today · 2022Review
- Immunotherapy in non-small cell lung cancer: Past, present, and future directions.Frontiers in oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune-checkpoint blockade has revolutionized cancer treatment. However, most patients do not respond to single-agent therapy. Combining checkpoint inhibitors with other immune-stimulating agents increases both efficacy and toxicity due to systemic T-cell activation. Protease-activatable antibody prodrugs, known as Probody therapeutics (Pb-Tx), localize antibody activity by attenuating capacity to bind antigen until protease activation in the tumor microenvironment. Herein, we show that systemic administration of anti-programmed cell death ligand 1 (anti-PD-L1) and anti-programmed cell death protein 1 (anti-PD-1) Pb-Tx to tumor-bearing mice elicited antitumor activity similar to that of traditional PD-1/PD-L1-targeted antibodies. Pb-Tx exhibited reduced systemic activity and an improved nonclinical safety profile, with markedly reduced target occupancy on peripheral T cells and reduced incidence of early-onset autoimmune diabetes in nonobese diabetic mice. Our results confirm that localized PD-1/PD-L1 inhibition by Pb-Tx can elicit robust antitumor immunity and minimize systemic immune-mediated toxicity. These data provide further preclinical rationale to support the ongoing development of the anti-PD-L1 Pb-Tx CX-072, which is currently in clinical trials.
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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.