Studies on the Effector Cells in Rejection of Syngeneic Murine C1300 Neuroblastoma

Abstract

It was difficult to obtain tumor resistance against murine C1300 neuroblastoma (C1300) in syngeneic hosts. We attempted to immunize A/J mice by weekly intraperitoneal injection of 2x10^6 Mitomycin Ctreated tumor cells as well as 200μg formalin-killed Corynebacterium parvum for 3 weeks. Approximately 70% of these mice were resistant to subsequent live tumor challenge of 10^5 cells. We used the spleen cells of these tumor resistant mice in Winn assay, adoptive chemoimmunotherapy and in vitro <51>^Cr-release assay. Winn assay demonstrated that immune spleen T cells had the capacity to reject the tumor. This cytotoxicity was partially eliminated by the treatment with ether anti-Lyt-1 or anti-Lyt-2 monoclonal antibody and complement. Administration of cyclophosphamide (I50mg/kg) and 5×10^7immune spleen cells into tumor-bearing hosts prolonged mean survival time. In 4-hour <51>^Cr-release assay, cytotoxic cells were detected in the immune spleen cells in 5-day Mixed lymphocyte tumor cell culture. Percent specific lysis of C1300 was over 40% (E : T = 40 : 1). These cells had no cytotoxicity against human neuroblastoma cells. These cytotoxic cells contained Thy-1^+ , Lyt-2^+ cells and Thy-1^+ , Lyt-1^- , Lyt-2^- cells. Anti-asialo-GM_1 antibody and complement could not eliminate cytotoxicity of these cells. Thy-1^+, Lyt-2^+ cells had specific cytotoxicity to C1300, and Thy-l^+, Lyt-1^-, Lyt-2^- cells had nonspecific killing ability. These data suggest the possibility of specific and nonspecific antitumor immunotherapy to neuroblastomas.