Tumor-specific delivery of biologics by a novel T-cell line HOZOT

Teppei Onishi, Hiroshi Tazawa, Yuuri Hashimoto, Makoto Takeuchi, Takeshi Otani, Shuji Nakamura, Fuminori Sakurai, Hiroyuki Mizuguchi, Hiroyuki Kishimoto, Yuzo Umeda, Yasuhiro Shirakawa, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Article number38060
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Nov 30 2016

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Biological Products
T-Lymphocytes
Cell Line
Neoplasms
Oncolytic Viruses
Neutralizing Antibodies
CD46 Antigens
Viral Antibodies
Virus Release
Biological Therapy
Telomerase
Fetal Blood
Adenoviridae

ASJC Scopus subject areas

  • General

Cite this

Tumor-specific delivery of biologics by a novel T-cell line HOZOT. / Onishi, Teppei; Tazawa, Hiroshi; Hashimoto, Yuuri; Takeuchi, Makoto; Otani, Takeshi; Nakamura, Shuji; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Kishimoto, Hiroyuki; Umeda, Yuzo; Shirakawa, Yasuhiro; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi.

In: Scientific Reports, Vol. 6, 38060, 30.11.2016.

Research output: Contribution to journalArticle

Onishi T, Tazawa H, Hashimoto Y, Takeuchi M, Otani T, Nakamura S et al. Tumor-specific delivery of biologics by a novel T-cell line HOZOT. Scientific Reports. 2016 Nov 30;6. 38060. https://doi.org/10.1038/srep38060
Onishi, Teppei ; Tazawa, Hiroshi ; Hashimoto, Yuuri ; Takeuchi, Makoto ; Otani, Takeshi ; Nakamura, Shuji ; Sakurai, Fuminori ; Mizuguchi, Hiroyuki ; Kishimoto, Hiroyuki ; Umeda, Yuzo ; Shirakawa, Yasuhiro ; Urata, Yasuo ; Kagawa, Shunsuke ; Fujiwara, Toshiyoshi. / Tumor-specific delivery of biologics by a novel T-cell line HOZOT. In: Scientific Reports. 2016 ; Vol. 6.
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