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Supplementary Figure 2 from CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains

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posted on 2023-04-03, 23:07 authored by Satoshi Shiina, Masasuke Ohno, Fumiharu Ohka, Shunichiro Kuramitsu, Akane Yamamichi, Akira Kato, Kazuya Motomura, Kuniaki Tanahashi, Takashi Yamamoto, Reiko Watanabe, Ichiro Ito, Takeshi Senga, Michinari Hamaguchi, Toshihiko Wakabayashi, Mika K. Kaneko, Yukinari Kato, Vidyalakshmi Chandramohan, Darell D. Bigner, Atsushi Natsume
<p>(A) Non-specific killing was also excluded by the observation that EGFRvIII-targeting (3C10)-CAR PBMCs did not display significant lysis to LN319 cells. (B) The FACS-sorted CAR-T cells were subjected to RT-PCR. TNF-α was significantly produced in NZ-1 CAR-T cells that were stimulated by LN319 cells, but IL-2 and CD107a were expressed even in mock CAR-T cells, which suggested that the secretion of IL-2 and CD107a was not specific to PDPN antigen.</p>

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Ministry of Education, Culture, Sports, Science, and Technology

PDIS, AMED and MEXT

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    DOI - Is supplement to CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains

ARTICLE ABSTRACT

Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults with a 5-year overall survival rate of less than 10%. Podoplanin (PDPN) is a type I transmembrane mucin-like glycoprotein, expressed in the lymphatic endothelium. Several solid tumors overexpress PDPN, including the mesenchymal type of GBM, which has been reported to present the worst prognosis among GBM subtypes. Chimeric antigen receptor (CAR)–transduced T cells can recognize predefined tumor surface antigens independent of MHC restriction, which is often downregulated in gliomas. We constructed a lentiviral vector expressing a third-generation CAR comprising a PDPN-specific antibody (NZ-1–based single-chain variable fragment) with CD28, 4-1BB, and CD3ζ intracellular domains. CAR-transduced peripheral blood monocytes were immunologically evaluated by calcein-mediated cytotoxic assay, ELISA, tumor size, and overall survival. The generated CAR T cells were specific and effective against PDPN-positive GBM cells in vitro. Systemic injection of the CAR T cells into an immunodeficient mouse model inhibited the growth of intracranial glioma xenografts in vivo. CAR T-cell therapy that targets PDPN would be a promising adoptive immunotherapy to treat mesenchymal GBM. Cancer Immunol Res; 4(3); 259–68. ©2016 AACR.

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