TY - JOUR
T1 - Tumor-specific delivery of biologics by a novel T-cell line HOZOT
AU - Onishi, Teppei
AU - Tazawa, Hiroshi
AU - Hashimoto, Yuuri
AU - Takeuchi, Makoto
AU - Otani, Takeshi
AU - Nakamura, Shuji
AU - Sakurai, Fuminori
AU - Mizuguchi, Hiroyuki
AU - Kishimoto, Hiroyuki
AU - Umeda, Yuzo
AU - Shirakawa, Yasuhiro
AU - Urata, Yasuo
AU - Kagawa, Shunsuke
AU - Fujiwara, Toshiyoshi
N1 - Publisher Copyright:
© 2016 The Author (S).
PY - 2016/11/30
Y1 - 2016/11/30
N2 - "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.
AB - "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.
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U2 - 10.1038/srep38060
DO - 10.1038/srep38060
M3 - Article
C2 - 27901098
AN - SCOPUS:84999880311
VL - 6
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 38060
ER -