AACR 2021: Double-humanized 4-1BB/4-1BBL mouse is an advanced model for liver toxicity and efficacy evaluation of 4-1BB therapeutic antibodies

AACR 2021: Double-humanized 4-1BB/4-1BBL mouse is an advanced model for liver toxicity and efficacy evaluation of 4-1BB therapeutic antibodies

Author: Lei Zhao, Linlin Wang, Dirui Li, Li Hui, Qingcong Lin

  • 4-1BB signaling results in increased cytotoxic T lymphocyte (CTL) activity, cytokine induction, and prevention of activation-induced cell death (AICD). 
  • Biocytogen generated a double humanized B-h4-1BB/h4-1BBL mouse model by replacing the exons encoding the mouse 4-1bb and 4-1bbl transmembrane and extracellular domains with the corresponding human exons. 
  • Anti-human 4-1BB antibodies significantly inhibited tumor growth in B-h4-1BB/h4-1BBL mice bearing MC38 tumor cells.
  • Compared to B-h4-1BB, double humanized B-h4-1BB/h4-1BBL mice have higher sensitivity on liver toxicity testing, reflected by sera AST and ALT levels, as well as liver pathological analysis. 
  • B-h4-1BB/h4-1BBL mice are a promising option for preclinical toxicity and efficacy evaluation of 4-1BB therapeutic antibodies. 

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