ArticleJournal of translational medicine2022
A humanized 4-1BB-targeting agonistic antibody exerts potent antitumor activity in colorectal cancer without systemic toxicity.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Comprehensive Review of Immunotherapy in Colorectal Cancer: From Mechanisms to Nursing Interventions.ImmunoTargets and therapy · 2026Review
- The role of tumor necrosis factor receptor superfamily in cancer: insights into oncogenesis, progression, and therapeutic strategies.NPJ precision oncology · 2025Review
- A humanized anti-MSLN×4-1BB bispecific antibody exhibits potent antitumour activity through 4-1BB signaling activation and fc function without systemic toxicity.Journal of translational medicine · 2025Article
- CD137-expressing regulatory T cells in cancer and autoimmune diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 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
- Review
- Immunotherapy-induced cytotoxic T follicular helper cells reduce numbers of retrovirus-infected reservoir cells in B cell follicles.PLoS pathogens · 2023Article
- 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
- A novel 4-1BB/HER2 bispecific antibody shows potent antitumor activities by increasing and activating tumor-infiltrating T cells.American journal of cancer research · 2023Article
- Exhausted T cells hijacking the cancer-immunity cycle: Assets and liabilities.Frontiers in immunology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer (CRC) is one of the most common malignancies and the patient survival rate remains unacceptably low. The anti-programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibody-based immune checkpoint inhibitors have been added to CRC treatment regimens, however, only a fraction of patients benefits. As an important co-stimulatory molecule, 4-1BB/CD137 is mainly expressed on the surface of immune cells including T and natural killer (NK) cells. Several agonistic molecules targeting 4-1BB have been clinically unsuccessful due to systemic toxicity or weak antitumor effects. We generated a humanized anti-4-1BB IgG4 antibody, HuB6, directed against a unique epitope and hypothesized that it would promote antitumor immunity with high safety.
methodsThe antigen binding specificity, affinity and activity of HuB6 were determined by enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), biolayer interferometry (BLI) and flow cytometry. The antitumor effects were evaluated in humanized mice bearing syngeneic tumors, and possible toxicity was evaluated in humanized mice and cynomolgus monkeys.
resultsHuB6 showed high specificity and affinity for a binding epitope distinct from those of other known 4-1BB agonists, including utomilumab and urelumab, and induced CD8 + T, CD4 + T and NK cell stimulation dependent on Fcγ receptor (FcγR) crosslinking. HuB6 inhibited CRC tumor growth in a dose-dependent manner, and the antitumor effect was similar with urelumab and utomilumab in humanized mouse models of syngeneic CRC. Furthermore, HuB6 combined with an anti-PD-L1 antibody significantly inhibited CRC growth in vivo. Additionally, HuB6 induced antitumor immune memory in tumor model mice rechallenged with 4 × 10
conclusionsThis study demonstrated that HuB6 should be a suitable candidate for further clinical development and a potential agent for CRC immunotherapy.
Indexed as
Identifiers
What OpenQuestion holds
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.