|Budget Amount *help
¥1,700,000 (Direct Cost : ¥1,700,000)
Fiscal Year 1991 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1990 : ¥800,000 (Direct Cost : ¥800,000)
The combinated anti-cancer treatment have been performed to improve the worse prognosis of patients with head and neck carcinoma. With the exception of curable treatments, operation and radiation therapy, the adequate combined cheno-immunotherapy and the precise administration timings of cheno-immuno therapeuetic drugs are obsuere. The immuno-enhansing ability of chenotherapy was examined. As the results, (1)At some period after chenotherapy, cheno-LAK cells which have LAK activity was induced. (2)ln in vitro examinations, the quantity of immunosuppressive factor which secreted from tumor cells treated with chemotherapeutic drugs was reduced and the inducibility of LAK cells by IL-2 was normalized with this reduction of suppressive factor. Furthermore, to autologous LAK cells, the sensitivity of treated tumor cells increased more than that of non-treated tumor cells. The supernate of mixed culture between treated tumor cells and effector cells, contained TNF-alpha, IFN-gamma and IL-1 b
eta. These cytokines could not be detected in mixed culture in which stimulator cells were non-treated tumor cells. These cytokines would augment autologous tumor cell killing of LAK cells, stimulated with treated tumor cells. Then, to clarify functions of previous endogeneous cytokines, the susceptibility of major histocompatibility(NHC)antigen expressed autologous head and neck tumors to lysis by LAX cells or TIL after treatment of the tumor cells with TNF-alpha, IFN-gamma and both these cytokines. MHC antigen expressed tumor cells were more sensitive than non-treated tumor cells to long term cultured autologous LAK cells. After treatment of VHC antigen expressed tumor cells with anti-class I Ag antibody, the susceptibility of this tumor cells was decreased. In addition, MUC expression of tumor cells markedly augmented the susceptibility to autologous TIL.
These results suggest the possibility of the synergistic effects between chemotherapy and immunotherapy. Hereafter, we will study the most effective chemotherapy on both sides, direct tumor cell killing and immuno-enhansingability, and devise the adequate combination therapy between chemotherapy and immunotherapy to improve the prognosis of patients with head and neck cancer. Less