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References
Hünig, T. The storm has cleared: lessons from the CD28 superagonist TGN1412 trial. Nature Rev. Immunol. 12, 317–318 (2012).
Proft, T. & Fraser, J. D. Bacterial superantigens. Clin. Exp. Immunol. 133, 299–306 (2003).
Horvath, C. J. & Milton, M. N. The TeGenero incident and the Duff Report conclusions: a series of unfortunate events or an avoidable event? Toxicol. Pathol. 37, 372–383 (2009).
Suntharalingam, G. et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N. Engl. J. Med. 355, 1018–1028 (2006).
Medicines and Healthcare Products Regulatory Agency. Clinical trial suspension: latest findings. MHRA [online], (2006).
Lühder, F . et al. Topological requirements and signaling properties of T cell-activating, anti-CD28 antibody superagonists. J. Exp. Med. 197, 955–966 (2003).
Tacke, M., Hanke, G., Hanke, T. & Hünig, T. CD28-mediated induction of proliferation in resting T cells in vitro and in vivo without engagement of the T cell receptor: evidence for functionally distinct forms of CD28. Eur. J. Immunol. 27, 239–247 (1997).
Lin, C. H. & Hünig, T. Efficient expansion of regulatory T cells in vitro and in vivo with a CD28 superagonist. J. Immunol. 33, 626–638 (2003).
Stebbings, R. et al. “Cytokine storm” in the phase I trial of monoclonal antibody TGN1412: better understanding the causes to improve preclinical testing of immunotherapeutics. J. Immunol. 179, 3325–3331 (2007).
Legrand, N. et al. Transient accumulation of human mature thymocytes and regulatory T cells with CD28 superagonist in “human immune system” Rag2−/−γc−/− mice. Blood 108, 238–245 (2006).
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH harmonized tripartite guideline S6: preclinical safety evaluation of biotechnology-derived pharmaceuticals (ICH, 1997).
US Food and Drug Administration Center for Drug Evaluation and Research. Guidance for industry. Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers (FDA, 2005).
Association of the British Pharmaceutical Industry/BioIndustry Association. Guideline for preclinical and clinical testing of new medicinal products. Parts 1 & 2 (ABPI, 1977).
Sims, J. & ABPI/BIA Early Stage Clinical Trials Task Force. Calculation of the minimum anticipated biological effect level (MABEL) and 1st dose in humans. EMA [online], (2007).
Lowe, P. J. et al. On the anticipation of the human dose in first-in-man trials from preclinical and prior clinical information in early drug development. Xenobiotica 37, 1331–1354 (2007).
Lowe, P. J., Tannenbaum, S., Wu, K., Lloyd, P. & Sims, J. On setting the first dose in man: quantitating biotherapeutic drug-target binding through pharmacokinetic and pharmacodynamic models. Basic Clin. Pharmacol. Toxicol. 106, 195–209 (2010).
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Horvath, C., Andrews, L., Baumann, A. et al. Storm forecasting: additional lessons from the CD28 superagonist TGN1412 trial. Nat Rev Immunol 12, 740 (2012). https://doi.org/10.1038/nri3192-c1
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DOI: https://doi.org/10.1038/nri3192-c1