Basic and clinical studies on induction of killer lymphocytes against neck and kidney tumors

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This study was made to develop the effective immune therapy for the tumors basing on the results of both basic and clinical researches concerning the induction of killer lymphocytes against neck and kidney tumors. As the clinical trials, Hayakawa M.D. tried to treat the patients with advanced renal cancer with the adoptive transfer of Lymphokine-activated killer (LAK) cells. He developed the regional arterial infusion therapy which yielded the excellent clinical results.On the other hand, in the basic approach, Tanabe M.D. and Koja M.D. developed the new method for the induction of the cytotoxic T lymphocytes (CTL) against the tumor cells. They also showed in this new system that the CTL recognized only the absolute dominant antigen which had the important role on the immunological self-nonself discrimination.(Basic approach)1. The bone marrow (BM) cells had the helper activity which augmented to induce the CTL from their precursors.2. Using the BM cells which had the helper effect, th … More e CTL specific to the minor-H antigen were induced easily in primary cultures in vitro. By the genetic analysis, the CTL recognized only the X-chromosome linked gene product (Xir) antigen) which had the important role on the self-nonself discrimination.3. Using the BM cells, the CTL specific to the tumor cells were induced easily in primary cultures in vitro. By the analysis of the rumor antigen recognized by these CTL, the tumor cells had lost the intrinsic Xir antigen which were expressed on normal original cells as described above. On the contrary, the tumor cells gained the new intrinsic Xir-like antigen on their surfaces.(Clinical approach)LAK cells and tumor infiltrating lymphocytes (TIL) were obtained from patients with advanced renal cell carcinoma (RCC). Those killer cells-mediated cytotoxicities against autologous tumor cell were nonspecific. Therefore, when they were systemically infused, they rarely reached metastatic sites of RCC. In contrast, regional arterial administration yielded a remarkable accumulation of killer cells in the tumor tissue and they stayed there for a certain period of time. LAK cell and TIL produced IFN-alpha and/or TNF-gamma when they were cultured with autologous tumor cells. The positive rate of these cytokines in the serum of the patients treated with LAK/IL-2 therapy was higher than that in the patients without LAK/IL-2 therapy. Seven out of 12 metastatic lesions in 12 patients with RCC treated with LAK/IL-2 therapy showed regression, whereas no clinical response was obtained with systemic LAK/IL-2 therapy. Regional arterial administration of killer cells seems to be worthwhile and promising for treatment of the advanced RCC as far as the mass production of the specific CTL to RCC is not presently available. Less