Retrovirally engineered T-cell-based immunotherapy targeting type III variant epidermal growth factor receptor, a glioma-associated antigen.

Abstract

The isotype of epidermal growth factor receptor variant III (EGFRvIII) is often identified in glioblastomas. Previously, we created a mouse monoclonal antibody, 3C10 (IgG2b), that specifically recognized EGFRvIII, and a recombinant single-chain variable fragment of 3C10. The aim of the current study was to develop genetically engineered T cells, termed T-bodies, that express a chimeric receptor consisting of the 3C10 single-chain variable fragment coupled to signaling modules such as the CD3zeta (ζ) chain, for the treatment of tumors expressing mutant EGFR. After successful construction of the chimeric 3C10/CD3ζ T-cell receptor, its expression on the T-body was observed using western blotting and flow cytometry. The specificity of the T-body for EGFRvIII was evaluated using an interferon-gamma Elispot assay and a standard (51) Cr-release cytotoxicity assay. Furthermore, we demonstrated that the systemically delivered T-body infiltrated the intrabrain tumor and significantly delayed tumor growth. These results indicate that the T-body expressing the chimeric 3C10/CD3ζ T-cell receptor specifically recognized glioma cells expressing EGFRvIII. In conclusion, T-body-based immunotherapy appears to be a promising approach for the treatment of glioma.

• Authors: Masasuke Ohno, Atsushi Natsume, Ken Ichiro Iwami, Hidetaka Iwamizu, Kana Noritake, Daiki Ito, Yuki Toi, Motokazu Ito, Kazuya Motomura, Jun Yoshida, Kazuhiro Yoshikawa, Toshihiko Wakabayashi
• Journal: Cancer science (Cancer Sci) Vol. 101 Issue 12 Pg. 2518-24 (Dec 2010) ISSN: 1349-7006 [Electronic] England
• PMID: 20880333 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 Japanese Cancer Association.

Chemical References

• Antigens, Neoplasm
• Receptors, Antigen, T-Cell
• Single-Chain Antibodies
• epidermal growth factor receptor VIII
• ErbB Receptors

Topics

• Animals
• Antigens, Neoplasm (immunology, therapeutic use)
• Blotting, Western
• Brain Neoplasms (immunology, therapy)
• Cell Line, Tumor
• Cell Separation
• Enzyme-Linked Immunospot Assay
• ErbB Receptors (antagonists & inhibitors)
• Female
• Flow Cytometry
• Genetic Engineering
• Glioma (immunology, therapy)
• Humans
• Immunotherapy (methods)
• Mice
• Mice, SCID
• Receptors, Antigen, T-Cell (genetics, immunology)
• Retroviridae
• Reverse Transcriptase Polymerase Chain Reaction
• Single-Chain Antibodies (immunology, therapeutic use)
• T-Lymphocytes (immunology)
• Xenograft Model Antitumor Assays