Carrier cell-mediated ovarian cancer-specific cellular and immunological gene therapy by induction of CTL

有复制能力的病毒已被开发用于治疗癌症。然而，它们的细胞毒性作用是不够的，因为它们的感染被中和抗体的产生所抑制。为了解决这一限制，我们开发了载体细胞系统来递送具有复制能力的腺病毒。溶瘤腺病毒AdE 3-IAI. 3B感染A549载体细胞可杀死靶癌细胞，且这种感染不受抗腺病毒抗体的抑制，可重复感染。在通过腺病毒免疫诱导抗腺病毒CTL应答后，施用感染有复制能力的腺病毒的载体细胞诱导完全肿瘤消退。腺病毒-GM-CSF通过增强抗腺病毒和抗肿瘤CTL应答增强了载体细胞的抗肿瘤作用。这种新型的载体细胞介导的病毒转染系统可能被证明在各种类型的癌症治疗中是有用的。

Replication-competent viruses have been developed to treat cancers. However, their cytotoxic effects are insufficient, because infection with them is inhibited by generation of neutralizing antibodies. To address this limitation, we developed carrier cell system to deliver a replication-competent adenovirus. A549 carrier cell infected with oncolytic adenovirus AdE3-IAI.3B killed target cancer cells and this infection was uninhibited by antiadenovirus antibody and enabled repetitive infection. After the induction of antiadenoviral CTL responses by immunization of adenovirus, administration of carrier cells infected with a replication-competent adenovirus induced complete tumor regression. Adenovirus-GM-CSF augmented the antitumor effect of carrier cells by increasing antiadenoviral and antitumoral CTL responses. This novel carrier cell-mediated viral transfection system might prove useful in a variety of types of cancer therapy.