Human PD-L1 Antibody - Atezolizumab IgG1fut Isotype

PD-L1 background

Programmed cell death ligand 1 (PD-L1), also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a transmembrane protein that can be constitutively expressed or induced in myeloid, lymphoid, and normal epithelial cells, as well as in cancer [1, 2]. PD-L1 is the principal ligand for programmed cell death protein 1 (PD-1) and under physiological conditions, this interaction is essential in the development of immune tolerance preventing excessive immune cell activity. However, PD-L1 expression is an immune evasion mechanism exploited by various malignancies and is generally associated with poorer prognosis [3]. Specifically, over-expressed PD-L1 on tumor cells and tumor-infiltrating immune cells, such as macrophages, can bind to PD-1 on cytotoxic T cells, and ultimately inhibit the anti-tumor T cell response [2, 4]. Thus, due to PD-L1’s instrumental role in immune evasion by cancer cells, there are numerous inhibitors in development as promising immuno-oncology therapies. Notably, Atezolizumab (also known as MPDL3280A), a fully humanized IgG1 (N298A) mAb that blocks the interaction of PD-L1 with PD-1 and induces anti-tumor immune reactivation, has been approved by the FDA for combinational use in the treatment of lung and breast cancer [2, 5].

References

1. Juneja, V.R. et al. 2017. PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. J Exp Med 214, 895-904.
2. Kythreotou, A. et al. 2018. PD-L1. J Clin Pathol 71, 189-194.
3. Sun, C. et al. 2018. Regulation and Function of the PD-L1 Checkpoint. Immunity 48, 434-452.
4. Lau, J. et al. 2017. Tumour and host cell PD-L1 is required to mediate suppression of anti-tumour immunity in mice. Nat Commun 8, 14572.
5. Heimes, A.S. & Schmidt, M. 2019. Atezolizumab for the treatment of triple-negative breast cancer. Expert Opin Investig Drugs 28, 1-5.