ArticleBlood2014
Anaphylaxis caused by repetitive doses of a GITR agonist monoclonal antibody in mice.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Antibody therapeutics with high affinity for FcγRs exacerbate anaphylaxis via FcγR-mediated capture by tumor-associated myeloid cells.Journal for immunotherapy of cancer · 2026Article
- TNFR2/CCR8 bispecific antibody enhances antitumor activity through depleting Ti-Tregs and boosting effector CD8Oncoimmunology · 2025Article
- Blood-brain barrier crossing biopolymer targeting c-Myc and anti-PD-1 activate primary brain lymphoma immunity: Artificial intelligence analysis.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Exploring the Role of GITR/GITRL Signaling: From Liver Disease to Hepatocellular Carcinoma.Cancers · 2024Review
- Tumor-associated neutrophils and macrophages exacerbate antidrug IgG-mediated anaphylactic reaction against an immune checkpoint inhibitor.Journal for immunotherapy of cancer · 2022Article
- Blood-brain barrier permeable nano immunoconjugates induce local immune responses for glioma therapy.Nature communications · 2019Article
- HERA-GITRL activates T cells and promotes anti-tumor efficacy independent of FcγR-binding functionality.Journal for immunotherapy of cancer · 2019Article
- Local Administration of GITR Agonistic Antibody Induces a Stronger Antitumor Immunity than Systemic Delivery.Scientific reports · 2019Article
- Regulatory T cells in the treatment of disease.Nature reviews. Drug discovery · 2018Review
- Cancer Immunotherapy: Factors Important for the Evaluation of Safety in Nonclinical Studies.The AAPS journal · 2018Review
- Anti-GITR Antibody Treatment Increases TCR Repertoire Diversity of Regulatory but not Effector T Cells Engaged in the Immune Response Against B16 Melanoma.Archivum immunologiae et therapiae experimentalis · 2017Article
- Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Repeated PD-1/PD-L1 monoclonal antibody administration induces fatal xenogeneic hypersensitivity reactions in a murine model of breast cancer.Oncoimmunology · 2016Article
- Improving Adoptive T Cell Therapy: The Particular Role of T Cell Costimulation, Cytokines, and Post-Transfer Vaccination.Frontiers in immunology · 2016Review
- GITR engagement in combination with CTLA-4 blockade completely abrogates immunosuppression mediated by human liver tumor-derived regulatory T cellsOncoimmunology · 2015Article
- Improved mouse models to assess tumour immunity and irAEs after combination cancer immunotherapies.Clinical & translational immunology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Immunotherapy for cancer using antibodies to enhance T-cell function has been successful in recent clinical trials. Many molecules that improve activation and effector function of T cells have been investigated as potential new targets for immunomodulatory antibodies, including the tumor necrosis factor receptor superfamily members GITR and OX40. Antibodies engaging GITR or OX40 result in significant tumor protection in preclinical models. In this study, we observed that the GITR agonist antibody DTA-1 causes anaphylaxis in mice upon repeated intraperitoneal dosing. DTA-1-induced anaphylaxis requires GITR, CD4(+) T cells, B cells, and interleukin-4. Transfer of serum antibodies from DTA-1-treated mice, which contain high levels of DTA-1-specific immunoglobulin G1 (IgG1), can induce anaphylaxis in naive mice upon administration of an additional dose of DTA-1, suggesting that anaphylaxis results from anti-DTA-1 antibodies. Depletion of basophils and blockade of platelet-activating factor, the key components of the IgG1 pathway of anaphylaxis, rescues the mice from DTA-1-induced anaphylaxis. These results demonstrate a previously undescribed lethal side effect of repetitive doses of an agonist immunomodulatory antibody as well as insight into the mechanism of toxicity, which may offer a means of preventing adverse effects in future clinical trials using anti-GITR or other agonist antibodies as immunotherapies.
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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.