| 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
|
| Resource |
| Human and Animal Cells |
ST2(RCB0224) |
