RRC ID 51954
Author 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.
Title Tumor-specific delivery of biologics by a novel T-cell line HOZOT.
Journal 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.
Volume 6
Pages 38060
Published 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
Times Cited 3
Human and Animal Cells ST2(RCB0224)