Preparing for first-in-man studies: the challenges for translational immunology post-TGN1412
Open accessAbstract
Current immunology research is generating many new approaches to immunotherapy. However, the recent disaster surrounding the testing of TGN1412, has unsettled regulators and the pharmaceutical industry regarding new immunotherapies and highlighted the complexities of conducting clinical trials with agents that target the immune system. Here we discuss the critical role for immunologists in ensuring that the development of new immunotherapies continues.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
TGN1412 was given at 1/500th the dose found safe in animal testing to 6 human volunteers in a phase I trial, rendering them all critically ill within minutes and leaving them all with long-term complications.
“An antibody to treat human autoimmune disease, TGN1412, was given at 1/500th the dose found safe in animal testing to 6 human volunteers in a phase I trial (30,31), rendering them all critically ill within minutes and leaving them all with long-term complications (32, 33, 34).”
From Limitations of Animal Studies for Predicting Toxicity in Clinical Trials (2019) · cites this paper as [31]
The paper’s Abstract and Table 1 describe TGN1412 as an anti-CD28 antibody tested in a Phase 1 study of healthy volunteers, with a starting dose calculated as a fraction of an animal-derived no-adverse-effect level. They do not give the claimed 1/500th fraction or specify six recipients. The subsequent claims about illness and long-term complications are attached to different citations in the citing sentence, so they are not assessed here. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412
Suntharalingam, G., Perry, M. R., Ward, S., Brett, S. J., Castello-Cortes, A., Brunner, M. D., & Panoskaltsis, N. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa063842 · Cited by 2,164 · see citing works
Establishing risk of human experimentation with drugs: lessons from TGN1412
Kenter, M., & Cohen, A. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69562-7 · Cited by 153 · see citing works
Flagged first, then by citations
Research works printed but not linked: 6
- Yousry TA, Major EO, Ryschkewitsch C et al. Evaluation of patients treated with natalizumab for progressive multifocal leu- koencephalopathy. N Engl J Med 2006; 354:924-33.
- Keymeulen B, Vandemeulebroucke E, Ziegler AG et al. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 2005; 352:2598-608.
- Dowsing T, Kendall MJ. The Northwick Park tragedy -protecting healthy volunteers in future first-in-man trials. J Clin Pharm Ther 2007; 32:203-7.
- Mehrishi JN, Szabo M, Bakacs T. Some aspects of the recom- binantly expressed humanised superagonist anti-CD28 mAb, TGN1412 trial catastrophe lessons to safeguard mAbs and vaccine trials. Vaccine 2007; 25:3517-23.
- Mitchell P. Critics pan timid European response to TeGenero disaster. Nat Biotechnol 2007; 25:485-6.
- Stobbart L, Murtagh MJ, Rapley T, Ford GA, Louw SJ, Rodgers H. We saw human guinea pigs explode. BMJ 2007; 334:566-7.
Cited by
Sorted by citations
Limitations of Animal Studies for Predicting Toxicity in Clinical Trials
Van Norman, G. A. (2019) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2019.10.008 · Cited by 709 · see citing works
TGN1412: From Discovery to Disaster
Attarwala, H. (2010) · Journal of Young Pharmacists · doi:10.4103/0975-1483.66810 · Cited by 253 · see citing works
“Adapted from Dayan and Wraith[8] TGN1412”
The Nuremberg Code subverts human health and safety by requiring animal modeling
Greek, R., Pippus, A., & Hansen, L. A. (2012) · BMC Medical Ethics · doi:10.1186/1472-6939-13-16 · Cited by 78 · see citing works
Safety of biologics, lessons learnt from TGN1412
Stebbings, R., Poole, S., & Thorpe, R. (2009) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2009.10.002 · Cited by 70 · see citing works
- Authors
- Dayan, C. M., & Wraith, D. C.
- Affiliations
- University of Bristol (GB)
- Corresponding author
- Dayan, C M
- Venue
- Clinical and Experimental Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-01-07
- Volume
- 151
- Issue
- 2
- Pages
- 231-234
- ISSN
- 0009-9104 (ISSN-L)
- 1365-2249
- PMC
- PMC2276942
- OpenAlex
- W1502349731
- Cited by
- 28
- References
- 2
- Citations by year
- 2025: 1 · 2022: 1 · 2019: 2 · 2018: 1 · 2016: 2 · 2014: 4 · 2012: 2
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical & Experimental Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- Wellcome Trust (074731)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- translational immunology, TGN1412, cytokine release syndrome, immunotherapy, clinical trial safety, regulatory challenges
- MeSH terms
- Antibodies, Monoclonal, Humans, Immunotherapy, Research Design, Risk Management, Clinical Trials, Phase I as Topic, Biomedical Research, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
