PO-426 Targeting of VEGFR2-expressing cells by chimeric antigen receptor (CAR) T cells for solid tumour therapy

• Published in: ESMO open Vol. 3; no. Suppl 2; pp. A397 - A398
• Main Authors: Huang, KJ, Hsiao, YH, Wu, TH, Huang, A, Ai, LS, Kuan, CT
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.07.2018
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1136/esmoopen-2018-EACR25.937

IntroductionIn the vascularisation process of neoplastic tissues, vascular endothelial growth factor (VEGF) and its receptors appear to be the dominant regulators of angiogenesis. Targeting of VEGFR-2 on endothelial cells has been one of the immunotherapeutic approaches to suppress pathologic angiogenesis and tumour growth in vivo. DCB has developed the anti-VEGFR2 antibodies and applied them in the approach of chimeric antigen receptor (CAR)-T cells for adoptive cellular immunotherapy of solid tumours.Material and methodsHuman T cells were infected by VEGFR2 CAR-lentivirus and were analysed for CAR expression. The antigen-specific activation and effector function were evaluated by culturing of CAR-T cells in the presence of VEGFR-2 expressing cells in vitro, including cytokine release, cell proliferation and specific target cell cytotoxicity. A human cancer xenograft animal model was used to evaluate the effecacy of these CAR-T cells.Results and discussionsT cells expressing the VEGFR-2 CARs mediated antigen-specific immune responses as revealed by IFN-γ production, cell proliferation and target cell lysis. A single dose of VEGFR-2 antigen-redirected T cells was potent in inhibiting the well-established and vascularized breast tumour growth.ConclusionThese VEGFR2 CAR-T cells exhibited the antigen-specific immune responses and the MHC-independent cell killing of target cells. This approach may provide an opportunity for the cellular gene therapy of various solid tumours.