Induction of acquired immunity in rats that have eliminated intracranial gliosarcoma cells by the expression of herpes simplex virus-thymidine kinase gene and ganciclovir administration.

Abstract

We examined a possible antitumor response against 9L rat gliosarcoma cells induced by the expression of the herpes simplex virus-thymidine kinase (HSV-TK) gene and the ganciclovir (GCV) system. Based on the amount of the major histocompatibility complex (MHC) class I antigens expressed on 9L cells transduced by the HSV-TK gene (9L/HSV-TK) we selected two clones (clones H and L), which represent high and low expressors of class I antigens, respectively. By means of serial magnetic resonance imaging we followed the change of tumor volumes of each clone in syngeneic rats, and found that the intracranial tumor growth was inversely correlated with the expression of MHC class I antigens, although in vitro growths of the clones remained unchanged. Moreover, histological examination revealed significant lymphocyte infiltration in the 9L/HSV-TK tumor of high MHC expression but not in the wild-type tumor. The therapeutic effect of GCV on them was not different, but we observed a prolonged survival of the rats which had eliminated 9L/HSV-TK clone L tumors by the treatment of GCV and were rechallenged with the same cells compared with the survival of naive rats inoculated with clone L cells. These data collectively suggest that the immune response operates even in the brain previously described as an immunologically privileged site.