CTLA4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152, competitively binds to B7-1 (CD80) and B7-2 (CD86) on Antigen-Presenting Cells (APCs) to block the T cell activating signal by B7 and CD28 (on T cells) interaction. The inhibition of CTLA4 by its inhibitory antibodies enhances T cell activity. The CTLA4 antibody is the first FDA- approved antibody to treat advanced melanoma.
mRNA Expression Analysis
RT-PCR analysis of CTLA4 gene. The hCTLA4, but not mCTLA4, mRNA was detected in splenocytes of the homozygous B-hCTLA4 mice.
Protein Expression Analysis
Splenocytes from both wild type (WT)C57BL/6 and homozygous B-hCTLA-4 mice were analyzed by flow cytometry for the expression of CTLA4. Mouse CTLA4+ T cells were detectable in the WT mice, while human CTLA4+ T cells were detectable in the homozygous B-hCTLA4 mice.
CTLA4 (Yervoy) mAb efficacy evaluation using murine colon
cancer MC38 cells
Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hCTLA4 mice. Mice were divided into control and treatment groups (n=5) when the tumor size was approximately 100 mm3. Three doses of the anti-hCTLA4 antibody Yervoy differentially inhibited tumor growth in the homozygous B-hCTLA4 mice, suggesting that B-hCTLA4 mouse model is an effective tool for in vivo hCTLA4 antibody efficacy studies. The average ± SEM of tumor sizes are shown in the figure. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM
1. Cell Research (2018) 0:1–15; doi: 10.1038/s41422-018-0012-z
3. Scientific Reports volume7, 42913 (2017) doi: 10.1038/srep42913