Development of a syngenic murine B16 cell line-derived melanoma susceptible to destruction by neuroattenuated HSV-1.

HSV-1 ICP34.5 mutants can slow progression of preformed tumors in rodent models. However, the current models available for study are limited due to the lack of a syngenic, low-immunogenic tumor model susceptible to HSV-1. Thus we have developed a new model to determine the role of the immune response in viral-mediated tumor destruction. The human herpesvirus entry (Hve) receptors (HveA, HveB, and HveC) and a control plasmid were transfected into B78H1 murine melanoma cells. Transfection of HveA and HveC conferred sensitivity to HSV-1 to these cells. A10 (HveA), C10 (HveC), and control cells were able to form tumors reproducibly in vivo. The transfection of the receptors into B78H1 cells did not induce a detectable in vivo immunogenicity to the tumors. Finally, A10 and C10 tumor-bearing mice treated with HSV-1 1716 had significant prolongation of survival compared to mock-treated mice. These data suggest that A10 and C10 will be useful as in vivo models for studying the role of the immune response in viral-mediated tumor destruction.