RT Journal Article
SR Electronic
T1 Discovery and preclinical characterization of the antagonist anti-PD-L1 monoclonal antibody LY3300054
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP 31
DO 10.1186/s40425-018-0329-7
VO 6
IS 1
A1 Yiwen Li
A1 Carmine Carpenito
A1 George Wang
A1 David Surguladze
A1 Amelie Forest
A1 Maria Malabunga
A1 Mary Murphy
A1 Yiwei Zhang
A1 Andreas Sonyi
A1 Darin Chin
A1 Douglas Burtrum
A1 Ivan Inigo
A1 Anthony Pennello
A1 Leyi Shen
A1 Laurent Malherbe
A1 Xinlei Chen
A1 Gerald Hall
A1 Jaafar N. Haidar
A1 Dale L. Ludwig
A1 Ruslan D. Novosiadly
A1 Michael Kalos
YR 2018
UL http://jitc.bmj.com/content/6/1/31.abstract
AB Background Modulation of the PD-1/PD-L1 axis through antagonist antibodies that block either receptor or ligand has been shown to reinvigorate the function of tumor-specific T cells and unleash potent anti-tumor immunity, leading to durable objective responses in a subset of patients across multiple tumor types.Results Here we describe the discovery and preclinical characterization of LY3300054, a fully human IgG1λ monoclonal antibody that binds to human PD-L1 with high affinity and inhibits interactions of PD-L1 with its two cognate receptors PD-1 and CD80. The functional activity of LY3300054 on primary human T cells is evaluated using a series of in vitro T cell functional assays and in vivo models using human-immune reconstituted mice. LY3300054 is shown to induce primary T cell activation in vitro, increase T cell activation in combination with anti-CTLA4 antibody, and to potently enhance anti-tumor alloreactivity in several xenograft mouse tumor models with reconstituted human immune cells. High-content molecular analysis of tumor and peripheral tissues from animals treated with LY3300054 reveals distinct adaptive immune activation signatures, and also previously not described modulation of innate immune pathways.Conclusions LY3300054 is currently being evaluated in phase I clinical trials for oncology indications.A correction to this article is available online at https://doi.org/10.1186/s40425-018-0354-6.