Human PD-L1 Antibody - Atezolizumab IgG1fut Isotype

Anti-human PD-L1 antibody - Human IgG1 non-fucosylated (high effector functions)

Anti-hPD-L1-hIgG1fut is a recombinant monoclonal antibody (mAb) featuring a variable region equivalent to Atezolizumab, which recognizes human (h)PD-L1, and a non-fucosylated constant region of the human IgG1 (hIgG1fut) isotype. Anti-hPD-L1-hIgG1fut is a non-fucosylated antibody, whereby the absence of fucose residues from N-glycans of the IgG-Fc results in an enhancement of antibody-dependent cellular cytotoxicity (ADCC). This increased ADCC is without any detectable change to complement-dependent cytotoxicity (CDC) or antigen-binding capability. Anti-hPD-L1-hIgG1fut was generated by recombinant DNA technology, produced in CHO cells (deficient for fucosylation), and purified by affinity chromatography with protein G.

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].

Key features of Anti-hPD-L1-hIgG1fut:

• Clinically relevant variable region targeting PD-L1
• Features the engineered hIgG1fut constant region for enhanced effector function (i.e. ADCC)
• Functionally validated by flow cytometry

The terms “Atezolizumab” and “MPDL3280A” are only used as references. Anti-hPD-L1-hIgG1fut is not a pharmaceutical biosimilar of Atezolizumab. It has not been developed nor approved by Atezolizumab owner(s), and is not intended for any therapeutic or diagnostic use in humans or animals.

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.