Lif As A Novel Cancer Immunotherapy Target: Modulating The Tumor Microenvironment With Msc-1, A Humanized Anti-Lif Monoclonal Antibody

Leukemia Inhibitory Factor (LIF) is a pleiotropic cytokine involved in many physiological and pathological processes. LIF is highly expressed in a subset of tumors across multiple tumor types and has been shown to correlate with poor prognosis. LIF is hypothesized to contribute to tumor growth and progression by acting on multiple aspects of cancer biology, including immunosuppression of the tumor microenvironment and is a key regulator of cancer initiating cells (CICs). MSC-1, a first-in-class, humanized monoclonal antibody (IgG1), is a potent and selective inhibitor of LIF. MSC-1 leads to STAT3 inhibition by disrupting LIF signaling through the LIF receptor (LIFR). Blocking LIF with MSC-1 decreased tumor growth in multiple mouse tumor models and drove reprogramming of the tumor microenvironment through modulation of immunosuppressive macrophages and of several immune cell types. These findings form the basis of a robust therapeutic hypothesis, whereby MSC-1 treatment may lead to clinical activity in multiple cancer indications. Clinical testing is planned to initiate in the end of 2017 and trials will incorporate target engagement and PD biomarkers as well as efficacy endpoints. Citation Format: Jeanne Magram, Naimish Pandya, Kimberly Hoffman, Robin Hallett, Patricia Giblin, Angus Sinclair, Judit Anido, Isabel Huber Ruano, Ada Sala, Monica Pascual, Vanessa Chigancas, Robert Wasserman, Joan Seoane. LIF as a novel cancer immunotherapy target: modulating the tumor microenvironment with MSC-1, a humanized anti-LIF monoclonal antibody [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr LB-B34.