Gene therapy for oral squamous cell carcinoma with IAI.3B promoter-driven oncolytic adenovirus-infected carrier cells

Abstract

Abstract. Although replication-competent oncolytic viral vectors have been developed to improve antitumor activity, the generation of high titers of neutralizing antibodies inhibits repetitive viral infection. Many studies have reported that oncolytic virus-infected carrier cells can overcome this viral induced immunogenicity. However, the effects of oncolytic virus-infected carrier cells in human oral squamous cell carcinoma (OSCC) have not yet been examined. In the present study, simulating the clinical trial, we examined the antitumor activity of carrier cells infected with oncolytic adenovirus AdE3-IAI.3B in human OSCC. IAI.3B was highly activated in OSCC cells but not in normal cells. AdE3-IAI.3B killed OSCC cells in vitro but not normal cells. AdE3-IAI.3B-infected A549 carrier cells eradicated OSCC GFP-SAS tumors in nude mice. Anti-adenovirus neutralizing antibodies completely blocked the antitumor effect of AdE3-IAI.3B but did not block that of carrier cells. After the induction of anti-adenoviral CTL responses by immunization of adenovirus, administration of carrier cells induced complete regression of murine squamous cell carcinoma SCC7 tumors. Adenovirus-GM-CSF augmented the antitumor effect of carrier cells. The IAI.3B-driven oncolytic adenovirus-infected carrier cell system might prove useful in the treatment of OSCC and clinical trials of it should be conducted in the near future.

Therapeutic properties of a vector carrying the HSV thymidine kinase and GM-CSF genes and delivered as a complex with a cationic copolymer

“…One of such means is activators of the host immune system, such as cytokines [82-84]. We used GM-CSF for this goal.…”