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Inhibition of PP2A with LB-100 Enhances Efficacy of CAR-T Cell Therapy Against Glioblastoma

1
Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
2
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
3
David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
4
Lixte Biotechnology Holdings, Inc., East Setauket, NY 11733, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 139; https://doi.org/10.3390/cancers12010139
Received: 13 November 2019 / Revised: 31 December 2019 / Accepted: 2 January 2020 / Published: 6 January 2020
Chimeric antigen receptor (CAR)-engineered T cells represent a promising modality for treating glioblastoma. Recently, we demonstrated that CAR-T cells targeting carbonic anhydrase IX (CAIX), a protein involved in HIF-1a hypoxic signaling, is a promising CAR-T cell target in an intracranial murine glioblastoma model. Anti-CAIX CAR-T cell therapy is limited by its suboptimal activation within the tumor microenvironment. LB-100, a small molecular inhibitor of protein phosphatase 2A (PP2A), has been shown to enhance T cell anti-tumor activity through activation of the mTOR signaling pathway. Herein, we investigated if a treatment strategy consisting of a combination of LB-100 and anti-CAIX CAR-T cell therapy produced a synergistic anti-tumor effect. Our studies demonstrate that LB-100 enhanced anti-CAIX CAR-T cell treatment efficacy in vitro and in vivo. Our findings demonstrate the role of LB-100 in augmenting the cytotoxic activity of anti-CAIX CAR-T cells and underscore the synergistic therapeutic potential of applying combination LB-100 and CAR-T Cell therapy to other solid tumors. View Full-Text
Keywords: CAR-T; LB-100; CAIX; PP2A; glioblastoma CAR-T; LB-100; CAIX; PP2A; glioblastoma
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Cui, J.; Wang, H.; Medina, R.; Zhang, Q.; Xu, C.; Indig, I.H.; Zhou, J.; Song, Q.; Dmitriev, P.; Sun, M.Y.; Guo, L.; Wang, Y.; Rosenblum, J.S.; Kovach, J.S.; Gilbert, M.R.; Zhuang, Z. Inhibition of PP2A with LB-100 Enhances Efficacy of CAR-T Cell Therapy Against Glioblastoma. Cancers 2020, 12, 139.

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