BTLA (B and T lymphocyte associated) is a B cell and T cell attenuator, another immune checkpoint negative regulator of the lg superfamily. It is structurally similar to CTLA4 and PD-1, and is expressed in B cells, T cells, NK cells, dendritic cells and macrophages. BTLA binds to its ligand HVEM (HVEM is a member of the tumor necrosis factor receptor superfamily) to transmit a co-inhibition signal in the body’s anti-tumor immune response , and is associated with the immune escape mechanism of the tumor. BTLA inhibitors enhance the TCR signaling pathway, restore T cell function, and is a potential novel target for tumor biotherapy.
mRNA Expression Analysis
RT-PCR analysis of B-hBTLA gene. The hBTLA, but not mBTLA, mRNA was detectable in splenocytes of the homozygous B-hBTLA mice.
Protein Expression Analysis
Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hBTLA mice were analyzed by flow cytometry. Mouse BTLA+ B cells were detectable in the WT C57BL/6 mice, while human BTLA+ B cells were detectable in the homozygous B-hBTLA mice.
Human BTLA mAb efficacy evaluation (MC38-hHVEM cell line)
Murine colon cancer MC38-hHVEM cells were subcutaneously implanted into homozygous B-hBTLA mice. Mice were grouped when the tumor size was approximately 150±50 mm3 (n=6). Two human BTLA antibodies inhibited tumor growth differently, confirming that the B-hBTLA mouse model is a powerful tool for in vivo BTLA antibody pharmacological efficacy studies. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.
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