RRC ID 51954
著者 Onishi T, Tazawa H, Hashimoto Y, Takeuchi M, Otani T, Nakamura S, Sakurai F, Mizuguchi H, Kishimoto H, Umeda Y, Shirakawa Y, Urata Y, Kagawa S, Fujiwara T.
タイトル Tumor-specific delivery of biologics by a novel T-cell line HOZOT.
ジャーナル Sci Rep
Abstract "Cell-in-cell" denotes an invasive phenotype in which one cell actively internalizes in another. The novel human T-cell line HOZOT, established from human umbilical cord blood, was shown to penetrate a variety of human cancer cells but not normal cells. Oncolytic viruses are emerging as biological therapies for human cancers; however, efficient viral delivery is limited by a lack of tumor-specific homing and presence of pre-existing or therapy-induced neutralizing antibodies. Here, we report a new, intriguing approach using HOZOT cells to transmit biologics such as oncolytic viruses into human cancer cells by cell-in-cell invasion. HOZOT cells were successfully loaded via human CD46 antigen with an attenuated adenovirus containing the fiber protein of adenovirus serotype 35 (OBP-401/F35), in which the telomerase promoter regulates viral replication. OBP-401/F35-loaded HOZOT cells were efficiently internalized into human cancer cells and exhibited tumor-specific killing by release of viruses, even in the presence of anti-viral neutralizing antibodies. Moreover, intraperitoneal administration of HOZOT cells loaded with OBP-401/F35 significantly suppressed peritoneally disseminated tumor growth in mice. This unique cell-in-cell property provides a platform for selective delivery of biologics into human cancer cells, which has important implications for the treatment of human cancers.
巻・号 6
ページ 38060
公開日 2016-11-30
DOI 10.1038/srep38060
PII srep38060
PMID 27901098
PMC PMC5129011
MeSH Cell Line, Tumor Genetic Vectors* Humans Membrane Cofactor Protein* Neoplasms / metabolism Neoplasms / pathology Neoplasms / therapy* Oncolytic Virotherapy / methods* Oncolytic Viruses* T-Lymphocytes / virology*
IF 3.998
引用数 3
リソース情報
ヒト・動物細胞 ST2(RCB0224)