ABSTRACT Immunotherapeutic strategies to cancer have focused on inducing tumor-specific immune response. The approach we have chosen involves direct genetic modification of tumors in situ, using two types of herpes simplex virus type 1 (HSV-1) vectors, recombinant HSV vectors and defective HSV vectors, as cancer vaccine. Recombinant virus vectors contain full-length HSV genomes in which various viral genes have been mutated and replaced by transgenes. Defective virus vectors are derived from plasmids containing two HSV cis-acting elements, origin of DNA replication and packaging sequence, and transcriptional unit to express the gene. In bilateral subcutaneous tumor models, unilateral intratumoral inoculation with a recombinant HSV vector, G207, caused a significant growth inhibition of both inoculated and contralateral non-inoculated tumors. To boost the antitumor activity by cancer vaccine with HSV, we have developed a defective HSV vector system containing G207 as a helper virus. Intratumoral inoculation with an IL-12 producing defective HSV vector/G207 induced very prominent local and systemic antitumor effect. These antitumor effects appear to be mediated by antitumor specific T cells generated with intratumoral HSV inoculation. The results suggest that HSV vectors can be used for in situ cancer vaccination by induction of a systemic antitumor immunity.
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