|Strain Name||C57BL/6-Pdcd1tm1(hPDCD1)Ctla4tm1(hCTLA4)/Bcgen||Common Name||B-hPD-1/hCTLA4 mice|
|Catalog number (Males)||BDM004M||Catalog number (Females)||BDM004F|
|PD-1(Programmed death-1) ；|
CTLA4 (Cytotoxic T-lymphocyte-associated protein 4,CD152)
mRNA expression analysis
Fig 1. RT-PCR analysis of the B-hPD-1/hCTLA4 humanized mice.
The splenocytes of the B-hPD-1/hCTLA4 homozygous mice showed expression of human PD-1 and CTLA4 mRNA but not mouse PD-1 and CTLA4 mRNA.
Protein expression analysis
Fig 2. Splenocytes from both wild t ype (WT) C57BL/6 and homozygous B-hPD-1 /hCTLA4 mice were analyzed by flow cytometry.
Mouse CTLA4+ T cells were detected in the WT mice, while human CTLA4+ T cells were detected in the homozygous B-hPD-1 /hCTLA4 mice.
Fig 3. Splenocytes from both wild t ype (WT) C57BL/6 and homozygous B-hPD-1 /hCTLA4 mice were analyzed by flow cytometry.
Mouse PD-1+ T cells were detected in the WT mice, while human PD-1+ T cells were detected in the homozygous B-hPD-1 /hCTLA4 mice.
Combination therapy of PD-1(Keytruda) Ab and CTLA4(Yervoy) Ab
Fig 4. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hCTLA4 mice. Mice were grouped when the tumor size was approximately 150±50 mm3 (n=5). Anti-hCTLA4 antibody Yervoy and the anti-hPD-1 antibody Keytruda show modest inhibition of tumor growth. On the other hand, combination of anti-hCTLA4 antibody Yervoy and the anti-hPD-1 antibody Keytruda shows almost complete inhibition when compared to single Ab treatment. B-hPD-1/hCTLA4 mouse model is a powerful tool for in vivo evaluation of combination therapy efficacy for hPD-1 antibodies and hCTLA4 antibodies . (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.