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Carrier Cell–mediated Delivery of a Replication-competent Adenovirus for Cancer Gene Therapy

2007; Elsevier BV; Volume: 15; Issue: 6 Linguagem: Inglês

10.1038/sj.mt.6300128

1525-0024

Katsuyuki Hamada, Junzo Desaki, Kou Nakagawa, Ting Zhang, Toshiro Shirakawa, Akinobu Gotoh, Masatoshi Tagawa,

CAR-T cell therapy research

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.