ArticleThe Journal of clinical investigation2014
Targeting CD137 enhances the efficacy of cetuximab.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 90 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
90 citing papers in PubMed, 161 citations in OpenAlex.
- A Phase II Efficacy and Safety, Open-Label, Multicenter Study of Imprime PGG Injection in Combination With Cetuximab in Patients With Stage IV KRAS-Mutant Colorectal Cancer.Clinical colorectal cancer · 2016Trial
- Article
- Signaling pathways in colorectal cancer implications for the target therapies.Molecular biomedicine · 2024Review
- CD137 costimulation is associated with reduced herpetic stromal keratitis and with developing normal CD8The Journal of general virology · 2022Article
- Current Trends in Precision Medicine and Next-Generation Sequencing in Head and Neck Cancer.Current treatment options in oncology · 2022Review
- Evaluating Human Natural Killer Cells Antibody-dependent Cellular Cytotoxicity (ADCC) Using Plate-bound Anti-CD16 Antibodies.Bio-protocol · 2022Article
- 4-1BB: A promising target for cancer immunotherapy.Frontiers in oncology · 2022Review
- Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies.Journal of experimental & clinical cancer research : CR · 2021Review
- Reovirus enhances cytotoxicity of natural killer cells against colorectal cancer via TLR3 pathway.Journal of translational medicine · 2021Article
- Improved therapeutic efficacy of unmodified anti-tumor antibodies by immune checkpoint blockade and kinase targeted therapy in mouse models of melanoma.Oncotarget · 2021Article
- Neoadjuvant immunotherapy in resectable head and neck cancer: oral cavity carcinoma as a potential research model.Therapeutic advances in medical oncology · 2021Review
- Novel Approaches to Improve Myeloma Cell Killing by Monoclonal Antibodies.Journal of clinical medicine · 2020Review
- Review
- Trispecific natural killer cell nanoengagers for targeted chemoimmunotherapy.Science advances · 2020Article
- Standard therapies: solutions for improving therapeutic effects of immune checkpoint inhibitors on colorectal cancer.Oncoimmunology · 2020Review
- CD137, an attractive candidate for the immunotherapy of lung cancer.Cancer science · 2020Review
- Nuclear-localized costimulatory molecule 4-1BBL promotes colon cancer cell proliferation and migration by regulating nuclear Gsk3β, and is linked to the poor outcomes associated with colon cancer.Cell cycle (Georgetown, Tex.) · 2020Article
- Immunogenomic correlates of response to cetuximab monotherapy in head and neck squamous cell carcinoma.Head & neck · 2019Article
- Review
- An Update on Anti-CD137 Antibodies in Immunotherapies for Cancer.International journal of molecular sciences · 2019Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retraction · 2019-06-03Concerns/Issues about Image · Investigation by Company/Institution ·
- Commented on by
- Retracted
Authors and funding
23 authors at 5 institutions in 3 countries.
Funding
Abstract
Treatment with cetuximab, an EGFR-targeting IgG1 mAb, results in beneficial, yet limited, clinical improvement for patients with head and neck (HN) cancer as well as colorectal cancer (CRC) patients with WT KRAS tumors. Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells contributes to the efficacy of cetuximab. The costimulatory molecule CD137 (4-1BB) is expressed following NK and memory T cell activation. We found that isolated human NK cells substantially increased expression of CD137 when exposed to cetuximab-coated, EGFR-expressing HN and CRC cell lines. Furthermore, activation of CD137 with an agonistic mAb enhanced NK cell degranulation and cytotoxicity. In multiple murine xenograft models, including EGFR-expressing cancer cells, HN cells, and KRAS-WT and KRAS-mutant CRC, combined cetuximab and anti-CD137 mAb administration was synergistic and led to complete tumor resolution and prolonged survival, which was dependent on the presence of NK cells. In patients receiving cetuximab, the level of CD137 on circulating and intratumoral NK cells was dependent on postcetuximab time and host FcyRIIIa polymorphism. Interestingly, the increase in CD137-expressing NK cells directly correlated to an increase in EGFR-specific CD8+ T cells. These results support development of a sequential antibody approach against EGFR-expressing malignancies that first targets the tumor and then the host immune system.
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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.