Oncolytic viral therapy for human colorectal cancer and liver metastases using a multi-mutated herpes simplex virus type-1 (G207)

G207 is a multi-mutated, replication-competent type-1 herpes simplex virus designed to target, infect, and lyse neurological tumors. This study examin es the feasibility of using G207 in the treatment of human colorectal cance r and defines the biological determinants of its antitumor efficacy. This v irus was tested on five human colorectal cancer cell lines in vitro to dete rmine efficacy of infection and tumor cell kill. These results were correla ted to measures of tumor cell proliferation. In vivo testing was performed through direct injections of G207 into xenografts of human colorectal cance r tumors grown in flanks of athymic rats. To evaluate an alternate method o f administration, hepatic portal vein infusion of G207 was performed in a s yngeneic model of liver metastases in Buffalo rats. Among the five cell lin es tested, infection rates ranged between 10% and 90%, which correlated dir ectly with S-phase fraction (8.6%-36.6%) and was proportional to response t o G207 therapy in vitro (1%-93%). Direct injection of G207 into nude rat fl ank tumors suppressed tumor growth significantly vs. control (0.58 +/- 0.60 cm(3) vs. 9.16 +/- 3.70 cm(3), P<0. 0001). In vivo tumor suppression corre lated with in vitro effect. In the syngeneic liver tumor model, portal infu sion resulted in significant reduction in number of liver nodules (13 +/- 1 0 nodules in G207-treated livers vs. 80 +/- 30 nodules in control livers, P <0.05). G207 infects and kills human colorectal cancer cells efficiently. I n vitro cytotoxicity assay and tumor S-phase fraction can be used to predic t response to treatment in vivo. This antineoplastic agent can be delivered effectively by both direct tumor injection and regional vascular infusion. G207 should be investigated further as therapy for colorectal cancer and l iver metastases.