T-cell immunoglobulin domain and mucin domain-3 (TIM3) is an activation-induced inhibitory molecule involved in immune tolerance and T-cell exhaustion in chronic viral infection and cancers. TIM3 maturation and cell surface expression is facilitated by forming a heterodimeric interaction with CD66a. Co- blockade of CD66a and TIM3 enhanced anti-tumor immune responses and eliminated tumors in mouse colorectal cancer models.
Protein Expression Analysis
Cells in ascites from both wild type (WT)C57BL/6 and homozygous B-hTIM3 mice were analyzed by flow cytometry. Mouse TIM3 + cells were detectable in non-T and non-B cells from the WT mice, while human TIM3 + cells were detectable in non-T and non-B cells from the homozygous B-hTIM3 mice.
Splenocytes from both wild type (WT)C57BL/6 and homozygous B-hTIM3 mice were analyzed by flow cytometry. Mouse TIM3 + T cells were detectable in the WT mice, while human TIM3 + T cells were detectable in the homozygous B-hTIM3 mice.
Human TIM3 mAb Efficacy Evaluation (MC38 cell line)
Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hTIM3 mice. Mice were divided into control and treatment groups (n = 5) when the tumor volume was about 150±50 mm3. The anti-human TIM3 antibody significantly inhibited tumor growth in homozygous B-hTIM3 mice, suggesting that the B-hTIM3 mouse model is an effective tool for in vivo hTIM3 antibody efficacy studies. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.
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