| Budget Amount *help |
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Research Abstract |
It has been know that human cancer cell is recognized by autologous T lymphocytes as an immunogen, resulting in immunologic response to induce autologous tumor killing activity. we have investigated during these 3 years whether the CTL specific to autologous tumor was also significantly induced, when the mixed tumor cell and lymphocyte culture (MLTC) was done with allogeneic tumor, which histology was identical to autologous tumor. Actually, squamous cell carcinoma, adenocarcinoma or adenoid cystic carcinoma cells either fresh or established as the cell line were treated with mitomycin C and cultured with peripheral blood lymphocytes followed by further culture with rll-2. Induced CTL was tested by cold target inhibition and MHC blocking ascertain the specificity of the CTL activity to autologous tumor, and consequently, the specificity was clearly proved in the study. Chlinical trials to use the in vitro induced CTL have also been done for therapeutic purpose. To observe the primary e
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ffect on reduction of the tumor mass, the induced CTL was infused back to the patient through the a feeding artery of the cancer. Seven out of 14 patients(50%) showed PR of CR by the CTL therapy alone, and a case with pulmonary metases of the squamous cell carcinoma received the therapy resulting in PR. From the results of basic and clinical studies, it could be concluded the allogeneic tumor cells either fresh or of the cell line are useful stimulator for in vitro induction of the CTL specific to autologous tumor, that surely is a resolution for a strict clinical limitation to use autologous tumor cells as the stimulator. It is obviously clear that the CTL therapy is significantly effective on reduction tumor mass with lesser side effects, however, it is also true that the CTL therapy alone hardly bring the patients into complete cure. Preliminary study for a combined therapy of the CTL with low dose chemotherapy, radiation and operation has been performed during a period of 1992. Up to present we have obtained the results that a marked enhancement of the CTL effect was observedby a pretreatment of low dose anticancer drug, and of radiation effect by a pretreatment of CTL. There fore, induction was done with combination of low dose chemotherapy and CTL, and followed by low dose irradiation. By the protocol, 6 patients with maxillary cancer were 4 for CR and 2 for PR, 3 cases with lingual cancer were all for PR, and one case with gingival cancer was PR. The effects were assured by the operation, which was certainly minimized. In the case of maxillary cancer, it has to be note that surgical removal of the orbital mass was avoidable by the combined therapy. The combined therapy including the CTL, therefore. could be big help to make higher the quality of life(QOL) of the head and neck cancer, although the study should be extended in future. Less
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