RGD-modified COX-2 promoter-controlled conditionally replicative adenovirus RGDCRAdCox2F

A conditionally replicative, oncolytic adenovirus type 5 (Ad5), with potential oncolytic activity. Arg-Gly-Asp (RGD)-modified cyclooxygenase (COX)-2 promoter-controlled conditionally replicative adenovirus (CRAd) RGDCRAdCox2F has been engineered to replace the original E1 region with a COX-2 promoter-controlled E1 expression cassette, and to include RGD modification of the fiber protein. Upon administration, the RGD motif of RGD-modified COX-2 CRAd RGDCRAdCox2F binds to integrins expressed on tumor cells. This results in the replication of the oncolytic adenovirus in tumor cells, which induces selective adenovirus-mediated cytotoxicity in tumor cells and leads to tumor cell lysis. Following the lysis of the infected cells, the oncolytic virus is released and infects adjacent cells. This induces further tumor cell oncolysis. The lysis of tumor cells also results in the release of tumor-associated antigens (TAAs) and inflammatory mediators, which may activate the immune system to mount an anti-tumor immune response. RGD modification of the fiber protein enhances the infectivity of the oncolytic virus. COX-2 promoter-controlled E1 expression regulates the replication of the oncolytic virus as COX-2 is overexpressed in gastrointestinal malignancies.