|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)
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
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.
人癌細胞に対し、自己リンパ球は抗原として認識、免疫応答の結果自己癌傷害活性が誘導されることが判っている。それはMHC拘束性ある自己癌特異的キラー細胞(CTL)であるが、自己癌と共通の他人(同種)の癌細胞抗原を認識、免疫応答の結果自己癌を傷害するCTLが誘導される事実を証明した。新鮮あるいは株化扁平上皮癌細胞、腺様嚢胞癌細胞等をマイトマイシンC処理し、他の担癌患者末梢血リンパ球と混合培養し、更にrIL-2と培養すると刺激原として用いた病理組織学的に同一の自己癌を傷害する活性化リンパ球(キラー細胞)が誘導され、cold target inhibitionの結果や、MHC拘束性のあることから特異性の高いCTLが誘導されたと判断された。この誘導されたCTLの臨床応用を目的に、まず、癌増殖局所に戻し注入し、癌縮小効果を観察した。この臨床応用は頭頚部に高率に発生する扁平上皮癌を対象とし上顎癌、歯齦癌舌癌、下咽頭癌、喉頭癌患者のそれぞれの栄養動脈を介して注入した。その結果、CTL単独のCR,PR効果は14例中7例(50%)であり、1例の肺転移巣に対する静脈注射の戻しでそれはPRであった。自己癌との混合培養によるCTL誘導に限界のあることから、同種癌細胞を利用できることは臨床適応拡大となり、治療学的に重要な結果を得たと判断した。しかし、本CTL療法単独による完全な癌制御は困難であることも確かであり、集学治療の中での本治療法の位置付けを検討することが重要である。平成4年度にはその検討を行い、手がかりとなる結果を得た。即ち、低濃度抗癌剤の使用を先行させるとCTLの効果が増強し、又、CTL治療の後、放射線感度が増強されることが判った。このプロトコールによる実際の臨床応用では上顎癌6例中4例がCR,2例がPRで100%、舌癌3例中PR3例で100%、歯齦癌1例でPRと高い効果が手術的にも確認された。眼球摘出を免れ、高いQOLを得る可能性も示唆された。 Less