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

已知人类癌细胞被自体T淋巴细胞识别为免疫原，产生免疫反应，诱导自体肿瘤杀伤活性。在这3年中，我们研究了在组织学上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，是否也能显著诱导出针对自体肿瘤的特异性CTL。实际上，无论是新鲜的鳞状细胞癌、腺癌还是腺样囊性癌细胞，都用丝裂霉素C处理，然后与外周血淋巴细胞培养，然后再用rll-2进一步培养。通过冷靶向抑制和MHC阻断检测诱导的CTL活性，以确定CTL活性对自体肿瘤的特异性，从而在本研究中明确了其特异性。使用体外诱导的CTL的临床试验也已用于治疗目的。要观察主要的e…诱导后的CTL通过肿瘤供血动脉回输给患者，对肿瘤质量有更好的抑制作用。14例患者中有7例(50%)单纯CTL治疗后出现PR，1例鳞癌肺转移患者接受CTL治疗后出现PR。基础和临床研究结果表明，无论是新鲜的异体肿瘤细胞还是该细胞系的同种异体肿瘤细胞都是体外诱导针对自体肿瘤的特异性CTL的有效刺激物，这无疑解决了使用自体肿瘤细胞作为刺激物的严格临床局限性。显然，CTL治疗在缩小肿瘤质量方面效果显著，副作用较小，但单用CTL治疗并不能完全治愈患者。1992年对小剂量化疗、放疗和手术联合治疗CTL进行了初步研究。结果表明，小剂量抗癌药物可显著增强CTL效应，CTL可显著增强辐射效应。因此，先用小剂量化疗联合CTL诱导，然后再进行低剂量照射。6例上颌癌CR 4例，PR 2例，舌癌3例全部PR，1例牙周癌PR。手术的效果得到了保证，当然也被降到了最低限度。在上颌癌的病例中，必须注意的是，通过综合治疗可以避免手术切除眼眶肿块。因此，包括CTL在内的综合治疗。这可能对提高头颈部癌症的生活质量(QOL)有很大帮助，尽管这项研究应该在未来扩大。较少

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