Gene targeting strategy of B-hPD-L1/hTIGIT mice. The exon 3 of mouse Pd-l1 gene that encodes the extracellular domain was replaced by human PD-L1 exon 3 in B-hPD-L1/hTIGIT mice. The exon 2 of mouse Tigit gene that encodes the extracellular domain was replaced by human TIGIT exon 2 in B-hPD-L1/hTIGIT mice.
Protein Expression Analysis
Splenocytes from B-hPD-L1/hTIGIT mice were analyzed by flow cytometry. mTIGIT+ cells were detectable in C57BL/6 mice, while hTIGIT+ cells were detectable in the homozygous B-hPD-L1/hTIGIT mice.
Splenocytes from B-hPD-L1/hTIGIT mice were analyzed by flow cytometry. mPD-L1+ cells were detectable in C57BL/6 mice, while hPD-L1+ cells were detectable in the homozygous B-hPD-L1/hTIGIT mice.
Antibody Efficacy Evaluation
Murine colon cancer MC38-hPD-L1 cells were subcutaneously implanted into homozygous B-hPD-L1/hTIGIT mice. Mice were grouped when the tumor size was approximately 150±50 mm3 (n=7). Combination of hTIGIT Ab and hPD-L1 Ab shows significantly inhibition when compared to single Ab treatment. B-hPD-L1/hTIGIT mouse model is a powerful tool for in vivo evaluation of combination therapy efficacy for hPD-L1 antibodies and hTIGIT antibodies. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.
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