PMID- 20880333 OWN - NLM STAT- MEDLINE DCOM- 20101215 LR - 20220408 IS - 1349-7006 (Electronic) IS - 1347-9032 (Linking) VI - 101 IP - 12 DP - 2010 Dec TI - Retrovirally engineered T-cell-based immunotherapy targeting type III variant epidermal growth factor receptor, a glioma-associated antigen. PG - 2518-24 LID - 10.1111/j.1349-7006.2010.01734.x [doi] AB - 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 (zeta) chain, for the treatment of tumors expressing mutant EGFR. After successful construction of the chimeric 3C10/CD3zeta 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/CD3zeta 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. CI - (c) 2010 Japanese Cancer Association. FAU - Ohno, Masasuke AU - Ohno M AD - Department of Neurosurgery, Nagoya University School of Medicine, Nagoya Center for Cell Therapy, Aichi Medical University, Nagakute, Aichi, Japan. FAU - Natsume, Atsushi AU - Natsume A FAU - Ichiro Iwami, Ken AU - Ichiro Iwami K FAU - Iwamizu, Hidetaka AU - Iwamizu H FAU - Noritake, Kana AU - Noritake K FAU - Ito, Daiki AU - Ito D FAU - Toi, Yuki AU - Toi Y FAU - Ito, Motokazu AU - Ito M FAU - Motomura, Kazuya AU - Motomura K FAU - Yoshida, Jun AU - Yoshida J FAU - Yoshikawa, Kazuhiro AU - Yoshikawa K FAU - Wakabayashi, Toshihiko AU - Wakabayashi T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100930 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (Antigens, Neoplasm) RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (Single-Chain Antibodies) RN - 0 (epidermal growth factor receptor VIII) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Animals MH - Antigens, Neoplasm/immunology/therapeutic use MH - Blotting, Western MH - Brain Neoplasms/immunology/*therapy MH - Cell Line, Tumor MH - Cell Separation MH - Enzyme-Linked Immunospot Assay MH - ErbB Receptors/*antagonists & inhibitors MH - Female MH - Flow Cytometry MH - Genetic Engineering MH - Glioma/immunology/*therapy MH - Humans MH - Immunotherapy/*methods MH - Mice MH - Mice, SCID MH - Receptors, Antigen, T-Cell/genetics/immunology MH - Retroviridae MH - Reverse Transcriptase Polymerase Chain Reaction MH - Single-Chain Antibodies/immunology/therapeutic use MH - T-Lymphocytes/*immunology MH - Xenograft Model Antitumor Assays EDAT- 2010/10/01 06:00 MHDA- 2010/12/16 06:00 CRDT- 2010/10/01 06:00 PHST- 2010/10/01 06:00 [entrez] PHST- 2010/10/01 06:00 [pubmed] PHST- 2010/12/16 06:00 [medline] AID - 10.1111/j.1349-7006.2010.01734.x [doi] PST - ppublish SO - Cancer Sci. 2010 Dec;101(12):2518-24. doi: 10.1111/j.1349-7006.2010.01734.x. Epub 2010 Sep 30.