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Correction to: Discovery and preclinical characterization of the antagonist anti-PD-L1 monoclonal antibody LY3300054

Authors :
Douglas Burtrum
Laurent Malherbe
David Surguladze
Dale L. Ludwig
Ruslan D. Novosiadly
Anthony Pennello
George Wang
Xinlei Chen
Yiwen Li
Gerald Hall
Mary Murphy
Ivan Inigo
Maria Malabunga
Leyi Shen
Darin Chin
Carmine Carpenito
Amelie Forest
Yiwei Zhang
Andreas Sonyi
Michael Kalos
Jaafar N. Haidar
Source :
Journal for ImmunoTherapy of Cancer, Vol 6, Iss 1, Pp 1-1 (2018), Journal for Immunotherapy of Cancer
Publication Year :
2018
Publisher :
BMJ, 2018.

Abstract

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. Electronic supplementary material The online version of this article (10.1186/s40425-018-0329-7) contains supplementary material, which is available to authorized users.

Details

ISSN :
20511426
Volume :
6
Database :
OpenAIRE
Journal :
Journal for ImmunoTherapy of Cancer
Accession number :
edsair.doi.dedup.....07b0f4b32b8d650a4e14496acaaa9c04
Full Text :
https://doi.org/10.1186/s40425-018-0354-6