Murine-Humanized Syngeneic Models for Antibody Evaluation

In vivo efficacy in WT mice that bearing commercialized murine cancer cells are widely used for early prove of conception for anti-mouse antibody on indicated targets.

(Table) Available murine cancer cells in LIDE. (Figure) MC38 murine colon cancer cells was inoculated into the right flank in C57BL/6J mice. Two anti-mPD-1 antibody, ab1 and ab2, were given at 5 mg/kg bi-weekly for 6 injections via i.v. or i.p., respectively, and demonstrated good anti-tumor effect.

In order to evaluate anti-human antibody, syngeneic model with both mice and murine cancer cells humanized should be constructed and applied accordingly.

(Left) Extracellular domain of both murine cancer cells (e.g.> PD-L1) and mice (e.g.> PD-1 on murine T cells) were replaced with humanized structure, while the promoter region asd well as intracellular signaling were maintained as previous. (Right) Flowchart of in vivo efficacy in humanized syngeneic models.

 

TAA1 overexpressed MC38 murine colon cancer cells (MC38-TAA1) was inoculated into the right flank in huPD-L1 transgenic mice. Both anti-huPD-L1 antibody (3 mg/kg, i.p., bi-weekly for 3 weeks) and anti-huPD-L1/TGFβ BsAb (3.6 mg/kg, i.p., bi-weekly for 3 weeks) demonstrated mediate anti-tumor effect.