Carrier cell-mediated delivery of a replication-competent adenovirus for cancer gene therapy.
Although replication-competent viruses have been developed to treat cancers, their cytotoxic effects are insufficient, as infection is inhibited by the generation of neutralizing antibodies. To address this limitation, we developed a carrier cell system to deliver a replication-competent adenovirus. Carrier cells infected with replication-competent adenovirus were incubated with target cancer cells in a high titer of anti-adenovirus antibody. Carrier cells were injected into syngeneic subcutaneous tumors after immunization with adenovirus. Carrier cell-derived cell fragments containing viral particles were engulfed by proliferative target cancer cells. This engulfment-mediated transfer of adenovirus was not inhibited by the anti-adenovirus antibody and enabled repetitive infection. After the induction of anti-adenoviral cytotoxic T-lymphocyte (CTL) responses by immunization with adenovirus, administration of carrier cells infected with a replication-competent adenovirus induced complete tumor regression. Adenovirus-GM-CSF augmented the anti-tumor effect of carrier cells by increasing anti-adenoviral and anti-tumoral CTL responses and decreased the number of injections of carrier cells required to induce complete tumor regression. This novel carrier cell-mediated viral transfection system might prove useful in a variety of cancer therapies.
Hamada
Katsuyuki
K
Department of Obstetrics and Gynecology, School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan. hamakatu@m.ehime-u.ac.jp
Desaki
Junzo
J
Nakagawa
Kou
K
Zhang
Ting
T
Shirakawa
Toshiro
T
Gotoh
Akinobu
A
Tagawa
Masatoshi
M
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology; D014779:Virus Replication / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D019496:Cancer Vaccines; D014765:Viral Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor