[Back to Issue 7 ToC] [Back to Journal Contents] [Back to Biochemistry (Moscow) Home page]

T-Cell Engagers Based Bioassay for Evaluation of PD-1/PD-L1 Inhibitors Activity

A. N. Doronin1,2, A. A. Gordeev1,2, A. E. Kozlov1, Ya. A. Smirnova1, M. Yu. Puchkova1,2, V. M. Ekimova1, Yu. I. Basovskiy1,2, and V. V. Solovyev1,2,a*

1BIOCAD, 142380 Lyubuchany, Moscow Region, Russia

2Pushchino State Institute of Natural Sciences, 142290 Pushchino, Moscow Region, Russia

* To whom correspondence should be addressed.

Received February 22, 2019; Revised April 17, 2019; Accepted April 18, 2019
PD-1/PD-L1-based therapy has been named a revolution in cancer treatment. By the end of 2018, more than 100 anti-PD-1 and anti-PD-L1 antibodies were in various stages of development, and more than 2000 clinical trials with their use have been registered. Characterization of such antibodies requires a bioassay to determine their biological activity. In this study, we developed a cell-based bioassay for analyzing the activity of anti-PD-1 and anti-PD-L1 antibodies. We chose reporter system consisting of two cell lines and compared several approaches for activation of effector cell line based on superantigens, soluble anti-CD3 antibodies, transmembrane anti-CD3 antibodies, chimeric antigenic receptors (CARs) and bispecific T-cell engager antibodies. The bispecific T-cell engager antibodies offer several advantages over the other approaches. We characterized the bioassay and demonstrated its applicability for analyzing the activity of anti-PD-1 and anti-PD-L1 antibodies. The proposed bioassay can be useful in the development of new therapeutic agents and methods for their characterization.
KEY WORDS: bioassay, PD-1, PD-L1, T-cell engager, CAR

DOI: 10.1134/S0006297919070034