Relevant preclinical models to test T cell engagers: the case of CD28
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Despite its ability to produce cytokines upon CD28 stimulation, the hCD28 mouse model is not recommended for safety and toxicity studies, due to its genetic design, as it might not trigger a cytokine release syndrome (CRS) with the same intensity than that in humans. Of note, genOway’s reconstituted mouse model BRGSF-HIS has proved most relevant to recapitulate CRS in a preclinical model.
The CD28 example perfectly illustrates the central importance of a relevant preclinical research model. Indeed, the choice of the most appropriate model entirely depends on the application. This is why genOway has developed and offers a set of catalog models fit for a variety of applications, including optimized models for T-cell-targeting bispecific antibodies and combination therapies.
References:
- Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, Panoskaltsis N. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006 Sep 7;355(10):1018-28.
- Porciello N, Tuosto L. CD28 costimulatory signals in T lymphocyte activation: Emerging functions beyond a qualitative and quantitative support to TCR signalling. Cytokine Growth Factor Rev. 2016 Apr;28:11-9.
- Lin CH, Hünig T. Efficient expansion of regulatory T cells in vitro and in vivo with a CD28 superagonist. Eur J Immunol. 2003 Mar;33(3):626-38.
- Porciello N, Grazioli P, Campese AF, Kunkl M, Caristi S, Mastrogiovanni M, Muscolini M, Spadaro F, Favre C, Nunès JA, Borroto A, Alarcon B, Screpanti I, Tuosto L. A non-conserved amino acid variant regulates differential signalling between human and mouse CD28. Nat Commun. 2018 Mar 14;9(1):1080.