ArticleJournal for immunotherapy of cancer2022
DuoBody-CD40x4-1BB induces dendritic-cell maturation and enhances T-cell activation through conditional CD40 and 4-1BB agonist activity.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04083599 (A First-in-Human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety and Anti-tumor Activity of GEN1042 in Subjects With Malignant Solid Tumors), which is not on this map. Cited by 30 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, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety and Anti-tumor Activity of GEN1042 in Subjects With Malignant Solid Tumors
Who cites it
30 citing papers in PubMed, 36 citations in OpenAlex.
- Dose Selection for DuoBody®-CD40x4-1BB (GEN1042/BNT312) Using a mPBPK/RO Model Leveraging Preclinical and Clinical Data.Clinical pharmacology and therapeutics · 2025Trial
- Review
- Agonistic bispecific antibodies: an emerging frontier in antibody therapeutics.Journal of translational medicine · 2026Review
- The global patent landscape of bispecific antibodies: technological innovations and therapeutic applications.Nature biotechnology · 2026Article
- Advancing immunotherapy via multiple immune cells co-engagement.Frontiers in immunology · 2026Review
- The emerging role of dendritic cells in the tumor microenvironment: from antigen presentation to targeted immunotherapy.Cell death & disease · 2025Review
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- The role of tumor necrosis factor receptor superfamily in cancer: insights into oncogenesis, progression, and therapeutic strategies.NPJ precision oncology · 2025Review
- Advances in molecular pathology and therapy of non-small cell lung cancer.Signal transduction and targeted therapy · 2025Review
- Emerging therapeutics targeting tumor-associated macrophages for the treatment of solid organ cancers.Expert opinion on emerging drugs · 2025Review
- Enhanced durability of a Zika virus self-amplifying RNA vaccine through combinatorial OX40 and 4-1BB agonism.JCI insight · 2025Article
- New insights into combined immunotherapy for hepatocellular carcinoma associated with liver cirrhosis.Frontiers in immunology · 2025Review
- Bispecific antibodies for multiple myeloma: past, present and future.International journal of hematology · 2024Review
- Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.Signal transduction and targeted therapy · 2024Review
- Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.Signal transduction and targeted therapy · 2024Review
- Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison.Molecular cancer · 2024Review
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- 4-1BB immunotherapy: advances and hurdles.Experimental & molecular medicine · 2024Review
- Bispecific antibodies tethering innate receptors induce human tolerant-dendritic cells and regulatory T cells.Frontiers in immunology · 2024Article
- Combining mathematical modeling,Frontiers in pharmacology · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
24 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite the preclinical promise of CD40 and 4-1BB as immuno-oncology targets, clinical efforts evaluating CD40 and 4-1BB agonists as monotherapy have found limited success. DuoBody-CD40×4-1BB (GEN1042/BNT312) is a novel investigational Fc-inert bispecific antibody for dual targeting and conditional stimulation of CD40 and 4-1BB to enhance priming and reactivation of tumor-specific immunity in patients with cancer.
methodsCharacterization of DuoBody-CD40×4-1BB in vitro was performed in a broad range of functional immune cell assays, including cell-based reporter assays, T-cell proliferation assays, mixed-lymphocyte reactions and tumor-infiltrating lymphocyte assays, as well as live-cell imaging. The in vivo activity of DuoBody-CD40×4-1BB was assessed in blood samples from patients with advanced solid tumors that were treated with DuoBody-CD40×4-1BB in the dose-escalation phase of the first-in-human clinical trial (NCT04083599).
resultsDuoBody-CD40×4-1BB exhibited conditional CD40 and 4-1BB agonist activity that was strictly dependent on crosslinking of both targets. Thereby, DuoBody-CD40×4-1BB strengthened the dendritic cell (DC)/T-cell immunological synapse, induced DC maturation, enhanced T-cell proliferation and effector functions in vitro and enhanced expansion of patient-derived tumor-infiltrating lymphocytes ex vivo. The addition of PD-1 blocking antibodies resulted in potentiation of T-cell activation and effector functions in vitro compared with either monotherapy, providing combination rationale. Furthermore, in a first-in-human clinical trial, DuoBody-CD40×4-1BB mediated clear immune modulation of peripheral antigen presenting cells and T cells in patients with advanced solid tumors.
conclusionDuoBody-CD40×4-1BB is capable of enhancing antitumor immunity by modulating DC and T-cell functions and shows biological activity in patients with advanced solid tumors. These findings demonstrate that targeting of these two pathways with an Fc-inert bispecific antibody may be an efficacious approach to (re)activate tumor-specific immunity and support the clinical investigation of DuoBody-CD40×4-1BB for the treatment of cancer.
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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.