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CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains.

Publication ,  Journal Article
Shiina, S; Ohno, M; Ohka, F; Kuramitsu, S; Yamamichi, A; Kato, A; Motomura, K; Tanahashi, K; Yamamoto, T; Watanabe, R; Ito, I; Senga, T ...
Published in: Cancer Immunol Res
March 2016

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.

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Published In

Cancer Immunol Res

DOI

EISSN

2326-6074

Publication Date

March 2016

Volume

4

Issue

3

Start / End Page

259 / 268

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Recombinant Fusion Proteins
  • Receptors, Antigen
  • Neoplasm Transplantation
  • Mice, SCID
  • Mice, Inbred NOD
  • Membrane Glycoproteins
  • Immunotherapy, Adoptive
  • Humans
  • Glioblastoma
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shiina, S., Ohno, M., Ohka, F., Kuramitsu, S., Yamamichi, A., Kato, A., … Natsume, A. (2016). CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains. Cancer Immunol Res, 4(3), 259–268. https://doi.org/10.1158/2326-6066.CIR-15-0060
Shiina, Satoshi, Masasuke Ohno, Fumiharu Ohka, Shunichiro Kuramitsu, Akane Yamamichi, Akira Kato, Kazuya Motomura, et al. “CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains.Cancer Immunol Res 4, no. 3 (March 2016): 259–68. https://doi.org/10.1158/2326-6066.CIR-15-0060.
Shiina S, Ohno M, Ohka F, Kuramitsu S, Yamamichi A, Kato A, et al. CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains. Cancer Immunol Res. 2016 Mar;4(3):259–68.
Shiina, Satoshi, et al. “CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains.Cancer Immunol Res, vol. 4, no. 3, Mar. 2016, pp. 259–68. Pubmed, doi:10.1158/2326-6066.CIR-15-0060.
Shiina S, Ohno M, Ohka F, Kuramitsu S, Yamamichi A, Kato A, Motomura K, Tanahashi K, Yamamoto T, Watanabe R, Ito I, Senga T, Hamaguchi M, Wakabayashi T, Kaneko MK, Kato Y, Chandramohan V, Bigner DD, Natsume A. CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains. Cancer Immunol Res. 2016 Mar;4(3):259–268.

Published In

Cancer Immunol Res

DOI

EISSN

2326-6074

Publication Date

March 2016

Volume

4

Issue

3

Start / End Page

259 / 268

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Recombinant Fusion Proteins
  • Receptors, Antigen
  • Neoplasm Transplantation
  • Mice, SCID
  • Mice, Inbred NOD
  • Membrane Glycoproteins
  • Immunotherapy, Adoptive
  • Humans
  • Glioblastoma