Study on induction of autologous CTL by mixed culture with allogeneic tumor cells.

已知人癌细胞被自体T淋巴细胞识别为免疫原，导致诱导自体肿瘤杀伤活性的免疫应答。在这3年中，我们研究了当用组织学与自体肿瘤相同的同种异体肿瘤进行混合肿瘤细胞和淋巴细胞培养（MLTC）时，是否也显著诱导了对自体肿瘤特异性的CTL。实际上，将新鲜的或建立为细胞系的鳞状细胞癌、腺癌或腺样囊性癌细胞用丝裂霉素C处理，并与外周血淋巴细胞一起培养，随后用rll-2进一步培养。通过冷靶点抑制和MHC阻断实验检测诱导的CTL活性，确定了CTL活性对自体肿瘤的特异性，从而明确了本研究中CTL活性的特异性。也已经进行了使用体外诱导的CTL用于治疗目的的临床试验。为了观察初级e 关于我们 为了观察诱导的CTL对肿瘤的缩小作用，将诱导的CTL通过肿瘤供血动脉回输给患者。14例单纯CTL治疗的患者中有7例（50%）出现PR或CR，1例肺鳞癌转移患者接受CTL治疗后出现PR。从基础和临床研究结果可以得出结论，新鲜同种异体肿瘤细胞或细胞系是体外诱导自体肿瘤特异性CTL的有效刺激物，这无疑是对使用自体肿瘤细胞作为刺激物的严格临床限制的解决方案。很明显，CTL治疗对减少肿瘤质量具有显著的效果，副作用较小，然而，单独的CTL治疗很难使患者完全治愈也是事实。在1992年期间进行了CTL与低剂量化疗、放疗和手术的联合治疗的初步研究。迄今为止，我们已获得的结果是，低剂量抗癌药物预处理可显著增强CTL效应，而CTL预处理可显著增强辐射效应。采用小剂量化疗加CTL诱导，再加小剂量照射。6例上颌癌患者中4例CR，2例PR，3例舌癌患者均PR，1例牙龈癌患者PR，手术效果得到了保证，手术量明显减少。在上颌骨癌的情况下，必须注意的是，手术切除眼眶肿块是可以避免的联合治疗。因此，包括CTL在内的联合治疗。对提高头颈部肿瘤患者的生活质量有重要意义，但仍需进一步研究。少

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 … More 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