Abstract
Replication-defective adenovirus（Ad） vectors played a pivotal role in the advancement of in vivo cancer gene therapy research during the 1990s. The development of conditionally replicated Ad （CRA）, i.e. the representative oncolytic virus（OV）, commenced during the 2000s, and research and clinical applications of CRAs armed with immune genes have been active in recent years. We developed a platform technology that can efficiently generate diverse types of “CRAs that can specifically target tumors with multiple factors”（m-CRAs） and survivin-responsive m-CRAs（Surv.m-CRAs） as innovative anticancer agents. Surv.m-CRA-1, which does not carry a therapeutic gene, is currently undergoing a multicenter, Phase II investigator-initiated clinical trial for early approval for malignant bone tumors. Moreover, we have recently identified a novel concept, “the need for optimal expression levels of immune transgene by optimal promoters,” in OVs armed with immune genes, to achieve both maximal therapeutic effects and the highest level of safety. In this review, we show Ad virology, the aforementioned points and discuss the potential for the next generation of CRAs.
