ArticleScientific reports2017
Improvement of Pharmacokinetic Profile of TRAIL via Trimer-Tag Enhances its Antitumor Activity in vivo.
Article in Scientific reports, 2017. 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 NCT04672395 (A Double-blind, Randomized, Controlled, Phase 2/3 Study to Evaluate the Efficacy, Immunogenicity, and Safety of CpG 1018/Alum-Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine), which is not on this map. Cited by 49 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 Double-blind, Randomized, Controlled, Phase 2/3 Study to Evaluate the Efficacy, Immunogenicity, and Safety of CpG 1018/Alum-Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine (SCB-2019) for the Prevention of SARS-CoV-2- Mediated COVID-19 in Participants Aged 12 Years and Older
Who cites it
49 citing papers in PubMed, 90 citations in OpenAlex.
- Safety and Efficacy of HexaBody-DR5/DR5 in Malignant Solid Tumors: Phase 1/2a Results and Translational Insights Into Observed Hepatotoxicity.Clinical and translational science · 2026Trial
- Trial
- Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomised, double-blind, placebo-controlled trial.Lancet (London, England) · 2021Trial
- Trimeric hemagglutinin vaccine provides chickens complete protection against lethal H5 subtype avian influenza virus from clade 2.3.4.4b.Emerging microbes & infections · 2026Article
- Genetically engineered macrophages delivering TRAIL targeting the Wnt/β-catenin pathway to induce cytotoxicity against TNBC.Cell communication and signaling : CCS · 2026Article
- Antineoplastic Activity of a Novel Trispecific Single-Chain Antibody Targeting the hERG1/β1 Integrin Complex and TRAIL Receptors.Molecular cancer therapeutics · 2025Article
- Using transcription and translation regulators to improve recombinant protein expression in CHO cells.Acta biochimica et biophysica Sinica · 2025Article
- Beyond Purification: Evolving Roles of Fusion Tags in Biotechnology.Current issues in molecular biology · 2025Review
- Turn TRAIL Into Better Anticancer Therapeutic Through TRAIL Fusion Proteins.Cancer medicine · 2025Review
- Recent Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Engineering Strategies for Precise Strike Therapy against Tumor.Biomaterials research · 2025Review
- A nucleoside-modified mRNA vaccine forming rabies virus-like particle elicits strong cellular and humoral immune responses against rabies virus infection in mice.Emerging microbes & infections · 2024Article
- TRAIL as a Warrior in Nano-Sized Trojan Horse: Anticancer and Anti-Metastatic Effects of Nano-Formulations of TRAIL in Cell Culture and Animal Model Studies.Medicina (Kaunas, Lithuania) · 2024Review
- Combination of multivalent DR5 receptor clustering agonists and histone deacetylase inhibitors for treatment of colon cancer.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Tumor necrosis factor superfamily signaling: life and death in cancer.Cancer metastasis reviews · 2024Review
- Auto-loaded TRAIL-exosomes derived from induced neural stem cells for brain cancer therapy.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Trimerized S expressed by modified vaccinia virus Ankara (MVA) confers superior protection against lethal SARS-CoV-2 challenge in mice.Journal of virology · 2024Article
- Suppression of neointimal hyperplasia induced by arteriovenous anastomosis and balloon injury in rats by multimeric tumor necrosis factor-related apoptosis-inducing ligand.Molecules and cells · 2024Article
- Remodeling tumor microenvironment using pH-sensitive biomimetic co-delivery of TRAIL/R848 liposomes against colorectal cancer.Oncology research · 2024Article
- Spike 1 trimer, a nanoparticle vaccine against porcine epidemic diarrhea virus induces protective immunity challenge in piglets.Frontiers in microbiology · 2024Article
- Aqueous Extract of Leaves and Flowers ofBiochemistry research international · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) has long been considered a tantalizing target for cancer therapy because it mediates activation of the extrinsic apoptosis pathway in a tumor-specific manner by binding to and trimerizing its functional receptors DR4 or DR5. Despite initial promise, both recombinant human TRAIL (native TRAIL) and dimeric DR4/DR5 agonist monoclonal antibodies (mAbs) failed in multiple human clinical trials. Here we show that in-frame fusion of human C-propeptide of α1(I) collagen (Trimer-Tag) to the C-terminus of mature human TRAIL leads to a disulfide bond-linked homotrimer which can be expressed at high levels as a secreted protein from CHO cells. The resulting TRAIL-Trimer not only retains similar bioactivity and receptor binding kinetics as native TRAIL in vitro which are 4-5 orders of magnitude superior to that of dimeric TRAIL-Fc, but also manifests more favorable pharmacokinetic and antitumor pharmacodynamic profiles in vivo than that of native TRAIL. Taken together, this work provides direct evidence for the in vivo antitumor efficacy of TRAIL being proportional to systemic drug exposure and suggests that the previous clinical failures may have been due to rapid systemic clearance of native TRAIL and poor apoptosis-inducing potency of dimeric agonist mAbs despite their long serum half-lives.
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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.