PT  - JOURNAL ARTICLE
AU  - Kotanides, Helen
AU  - Li, Yiwen
AU  - Malabunga, Maria
AU  - Carpenito, Carmine
AU  - Eastman, Scott W.
AU  - Shen, Yang
AU  - Wang, George
AU  - Inigo, Ivan
AU  - Surguladze, David
AU  - Pennello, Anthony L.
AU  - Persaud, Krishnadatt
AU  - Hindi, Sagit
AU  - Topper, Michael
AU  - Chen, Xinlei
AU  - Zhang, Yiwei
AU  - Bulaon, Danielle K.
AU  - Bailey, Tim
AU  - Lao, Yanbin
AU  - Han, Bing
AU  - Torgerson, Stacy
AU  - Chin, Darin
AU  - Sonyi, Andreas
AU  - Haidar, Jaafar N.
AU  - Novosiadly, Ruslan D.
AU  - Moxham, Christopher M.
AU  - Plowman, Gregory D.
AU  - Ludwig, Dale L.
AU  - Kalos, Michael
TI  - Bispecific Targeting of PD-1 and PD-L1 Enhances T-cell Activation and Antitumor Immunity
AID  - 10.1158/2326-6066.CIR-20-0304
DP  - 2020 Oct 01
TA  - Cancer Immunology Research
PG  - 1300--1310
VI  - 8
IP  - 10
4099  - http://cancerimmunolres.aacrjournals.org/content/8/10/1300.short
4100  - http://cancerimmunolres.aacrjournals.org/content/8/10/1300.full
SO  - Cancer Immunol Res2020 Oct 01; 8
AB  - The programmed cell death protein 1 receptor (PD-1) and programmed death ligand 1 (PD-L1) coinhibitory pathway suppresses T-cell–mediated immunity. We hypothesized that cotargeting of PD-1 and PD-L1 with a bispecific antibody molecule could provide an alternative therapeutic approach, with enhanced antitumor activity, compared with monospecific PD-1 and PD-L1 antibodies. Here, we describe LY3434172, a bispecific IgG1 mAb with ablated Fc immune effector function that targets both human PD-1 and PD-L1. LY3434172 fully inhibited the major inhibitory receptor–ligand interactions in the PD-1 pathway. LY3434172 enhanced functional activation of T cells in vitro compared with the parent anti–PD-1 and anti–PD-L1 antibody combination or respective monotherapies. In mouse tumor models reconstituted with human immune cells, LY3434172 therapy induced dramatic and potent antitumor activity compared with each parent antibody or their combination. Collectively, these results demonstrated the enhanced immunomodulatory (immune blockade) properties of LY3434172, which improved antitumor immune response in preclinical studies, thus supporting its evaluation as a novel bispecific cancer immunotherapy.