Systemic antitumor immunity in experimental brain tumor therapy using a multimutated, replication-competent herpes simplex virus

Replication-competent, attenuated herpes simplex virus (HSV) vectors have b een developed for viral oncolytic therapy of primary and metastatic maligna nt brain tumors. However, the role of the host immune responses in the brai n has not been elucidated. N18 neuroblastoma cells mere used as a tumor mod el in syngeneic A/J mice to test the therapeutic efficacy of G207, a condit ionally replicating HSV vector, in an immunocompetent condition. G207 inocu lated intraneoplastically exhibited a prominent oncolytic antitumor effect in mice harboring N18 tumors in the brain or subcutaneously, and, in additi on, elicited a systemic antitumor immune response, Subcutaneous tumor thera py with G207 caused regression of a remote, established tumor in the brain or in the periphery, which was potentially mediated hy the systemic antitum or immune response, and provided persistent tumor-specific protection again st N18 tumor rechallenge in the brain as well as in the periphery. Antitumo r immunity was associated with an elevation of specific CTL activity agains t N18 tumor cells that persisted for at least 13 months. The results sugges t that the oncolytic antitumor action of replication-competent HSV may be a ugmented by induction of specific and systemic antitumor immunity effective both in the periphery and in the brain.