ArticleNature communications2021
Cancer immune therapy with PD-1-dependent CD137 co-stimulation provides localized tumour killing without systemic toxicity.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Review
- Selective elimination of circulating effector CD8 T cells via LTβR blockade separates anti-CD137 efficacy from toxicity.Science advances · 2026Article
- Development of a nanoparticle-based immunotherapy targeting CD137 for nasopharyngeal carcinoma treatment.Theranostics · 2026Article
- Non-classical immune checkpoint CD137/CD137L and CD200/CD200R expressions are regulated by the tumor immune microenvironment in lymph node aspirates from lung cancer patients.Frontiers in immunology · 2026Article
- Can Immune Checkpoint Modulation Redefine Ocular Immunotherapy? Emerging Mechanisms, Challenges, and Translational Opportunities-A Comprehensive Review.Investigative ophthalmology & visual science · 2025Review
- Therapeutic targeting of cell death-immune crosstalk in cancer to rewire the tumor immune microenvironment.Molecular cancer · 2025Review
- CD137-expressing regulatory T cells in cancer and autoimmune diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Immunophenotyping of septic shock patients with endotheliopathy: focus on monocyte subtypes and Immune regulatory molecules.Frontiers in immunology · 2025Article
- A mechanistic quantitative systems pharmacology model platform for translational efficacy evaluation and checkpoint combination design of bispecific immuno-modulatory antibodies.Frontiers in pharmacology · 2025Article
- CD34International journal of hematology · 2025Article
- Immunotherapy resistance in solid tumors: mechanisms and potential solutions.Cancer biology & therapy · 2024Review
- Design of Crosslinking Antibodies For T-Cell Activation: Experimental and Computational Analysis of PD-1/CD137 Bispecific Agents.The AAPS journal · 2024Article
- Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.Signal transduction and targeted therapy · 2024Review
- Upregulation of HLA-II related to LAG-3Cancer science · 2024Article
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Anti-Tumor Potential of Post-Translational Modifications of PD-1.Current issues in molecular biology · 2024Review
- Peritumoral administration of immunomodulatory antibodies as a triple combination suppresses skin tumor growth without systemic toxicity.Journal for immunotherapy of cancer · 2024Article
- Effective cancer immunotherapy combining mRNA-encoded bispecific antibodies that induce polyclonal T cell engagement and PD-L1-dependent 4-1BB costimulation.Frontiers in immunology · 2024Article
- An Fc-muted bispecific antibody targeting PD-L1 and 4-1BB induces antitumor immune activity in colorectal cancer without systemic toxicity.Cellular & molecular biology letters · 2023Article
- Agonism of 4-1BB for immune therapy: a perspective on possibilities and complications.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expression of the cell surface receptor CD137 has been shown to enhance anti-cancer T cell function via engagement with its natural ligand 4-1BBL. CD137 ligation with engineered ligands has emerged as a cancer immunotherapy strategy, yet clinical development of agonists has been hindered by either toxicity or limited efficacy. Here we show that a CD137/PD-1 bispecific antibody, IBI319, is able to overcome these limitations by coupling CD137 activation to PD-1-crosslinking. In CT26 and MC38 syngeneic mouse tumour models, IBI319 restricts T cell co-stimulation to PD-1-rich microenvironments, such as tumours and tumour-draining lymph nodes, hence systemic (liver) toxicity arising from generalised T cell activation is reduced. Besides limiting systemic T cell co-stimulation, the anti-PD-1 arm of IBI319 also exhibits checkpoint blockade functions, with an overall result of T and NK cell infiltration into tumours. Toxicology profiling in non-human primates shows that IBI319 is a well-tolerated molecule with IgG-like pharmacokinetic properties, thus a suitable candidate for further clinical development.
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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.