ArticleJournal for immunotherapy of cancer2019
The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03782467 (A First-in-human, Multicenter, Open-label, Phase 1 Study in Patients With Advanced and/or Refractory Solid Malignancies to Evaluate the Safety of Intravenously Administered ATOR-1015), which is not on this map. Cited by 67 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.
A First-in-human, Multicenter, Open-label, Phase 1 Study in Patients With Advanced and/or Refractory Solid Malignancies to Evaluate the Safety of Intravenously Administered ATOR-1015
Who cites it
67 citing papers in PubMed, 112 citations in OpenAlex.
- Review
- First-in-human study of intravenous bispecific CTLA-4 × OX40 antibody (ATOR-1015) in advanced solid malignancies.ESMO open · 2026Article
- Targeting tumor-infiltrating regulatory T cells based on immunometabolism.Cancer biology & medicine · 2026Review
- OX40 signaling in cancer immunotherapy: mechanisms of action, translational applications, and therapeutic perspectives.Frontiers in immunology · 2026Review
- TNFR2/CCR8 bispecific antibody enhances antitumor activity through depleting Ti-Tregs and boosting effector CD8Oncoimmunology · 2025Article
- Advancing In Vivo Detection of T-Cell Function: Development and Preclinical Evaluation ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects.Journal of hematology & oncology · 2025Review
- Unraveling Th subsets: insights into their role in immune checkpoint inhibitor therapy.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- A mechanistic quantitative systems pharmacology model platform for translational efficacy evaluation and checkpoint combination design of bispecific immuno-modulatory antibodies.Frontiers in pharmacology · 2025Article
- The Evolving Applications of Bispecific Antibodies: Reaping the Harvest of Early Sowing and Planting New Seeds.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- CTLA-4-two pathways to anti-tumour immunity?Immunotherapy advances · 2025Review
- Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.International journal of biological sciences · 2025Review
- SHR-1806, a robust OX40 agonist to promote T cell-mediated antitumor immunity.Cancer biology & therapy · 2024Article
- A CD25×TIGIT bispecific antibody induces anti-tumor activity through selective intratumoral Treg cell depletion.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Targeting cytotoxic lymphocyte antigen 4 (CTLA-4) in breast cancer.European journal of medical research · 2024Review
- Bispecific and multispecific antibodies in oncology: opportunities and challenges.Nature reviews. Clinical oncology · 2024Review
- Current and future immunotherapeutic approaches in pancreatic cancer treatment.Journal of hematology & oncology · 2024Review
- Cancer therapy with antibodies.Nature reviews. Cancer · 2024Review
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- Evaluation of regulatory T-cells in cancer immunotherapy: therapeutic relevance of immune checkpoint inhibition.Medical oncology (Northwood, London, England) · 2024Review
7 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
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe CTLA-4 blocking antibody ipilimumab has demonstrated substantial and durable effects in patients with melanoma. While CTLA-4 therapy, both as monotherapy and in combination with PD-1 targeting therapies, has great potential in many indications, the toxicities of the current treatment regimens may limit their use. Thus, there is a medical need for new CTLA-4 targeting therapies with improved benefit-risk profile.
methodsATOR-1015 is a human CTLA-4 x OX40 targeting IgG1 bispecific antibody generated by linking an optimized version of the Ig-like V-type domain of human CD86, a natural CTLA-4 ligand, to an agonistic OX40 antibody. In vitro evaluation of T-cell activation and T regulatory cell (Treg) depletion was performed using purified cells from healthy human donors or cell lines. In vivo anti-tumor responses were studied using human OX40 transgenic (knock-in) mice with established syngeneic tumors. Tumors and spleens from treated mice were analyzed for CD8
resultsATOR-1015 induces T-cell activation and Treg depletion in vitro. Treatment with ATOR-1015 reduces tumor growth and improves survival in several syngeneic tumor models, including bladder, colon and pancreas cancer models. It is further demonstrated that ATOR-1015 induces tumor-specific and long-term immunological memory and enhances the response to PD-1 inhibition. Moreover, ATOR-1015 localizes to the tumor area where it reduces the frequency of Tregs and increases the number and activation of CD8
conclusionsBy targeting CTLA-4 and OX40 simultaneously, ATOR-1015 is directed to the tumor area where it induces enhanced immune activation, and thus has the potential to be a next generation CTLA-4 targeting therapy with improved clinical efficacy and reduced toxicity. ATOR-1015 is also expected to act synergistically with anti-PD-1/PD-L1 therapy. The pre-clinical data support clinical development of ATOR-1015, and a first-in-human trial has started (NCT03782467).
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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.