Development of a tumor cell bank for next generation immunotherapy

本研究的目的是开发一种高度成功的程序来建立符合输血安全标准的肿瘤细胞系，并建立一个系统，将这些肿瘤细胞用于治疗其他人（用于治疗的肿瘤细胞库）。本研究期间获得的数据总结如下：1。肿瘤细胞系的建立：1)制备96孔培养微孔板，每孔含有不同浓度的自体血清或积液。利用该微孔板，从32例新鲜癌组织中成功建立了6株肿瘤细胞系。2)利用微重力培养系统对肿瘤组织中存在的肿瘤细胞进行了长期培养。肿瘤细胞治疗登记（肿瘤细胞库）：在6个肿瘤细胞系中，我们获得了5个患者的肿瘤细胞库登记许可。虽然我们获得了其他4名患者的注册许可，但我们并没有成功建立肿瘤细胞系。这些肿瘤组织作为伴生肿瘤细胞冷冻保存，等待治疗。肿瘤细胞库的临床应用：在接受自体肿瘤脉冲树突状细胞疫苗治疗的3例患者中，有2例判断可以使用注册为肿瘤细胞库的非自体肿瘤细胞代替自体肿瘤细胞。在一个用完自身肿瘤细胞的患者中，继续使用在肿瘤细胞库中登记的非自身肿瘤细胞进行疫苗治疗。经过一段时间的治疗，抗肿瘤免疫反应保持良好，未发现特别的副作用。肿瘤细胞库的宣传：我们在主页（http://www.tumor.med.kyushu-u.ac.jp/）.5)上展示了我们树突状细胞疫苗治疗的临床数据，并介绍了肿瘤细胞库。利用登记在肿瘤细胞库的肿瘤细胞分泌的gmp级外泌体进行无细胞疫苗治疗的可能性。

Purpose of this study is to develop a highly successful procedure for establishing tumor cell lines which conform to safety criteria of blood transfusion and to build a system to use these tumor cells for treatment of other humans (a tumor cell bank for treatments).Data obtained during this study period are summarized as follows :1.Establishment of tumor cell lines for treatment :1)We prepared a 96-well culture microplate in which each wells contain different concentrations of autologous sera or effusions. By using this microplate, 6 tumor cell lines were successfully established from 32 fresh carcinoma tissues.2)We succeeded in long-term culture of tumor cells existing in tumor tissue by using micro-gravity culture system.2.Registration of tumor cells for treatment (tumor cell bank) :Among the 6 tumor cell lines, we got registration permission from five patients as a tumor cell bank.Although we got registration permission from other 4 patients, we did not succeed in the establishment of a tumor cell line. These tumor tissues were frozen and stored as associate tumor cells for treatment.3.Clinical application of tumor cell bank :In 2 of 3 patients who are undergoing self tumor-pulsed dendritic cell-based vaccine therapy, it was judged to be able to use non-self tumor cells registered as tumor cell bank instead of self tumor cells.In one patient who used up self tumor cells, the vaccine therapy was continued by using non-self tumor cells registered to tumor cell bank. Through a treatment period, an antitumor immune response was maintained well, and no particular side effect was recognized.4.Publicity of tumor cell bank :We showed clinical data of our dendritic cell-based vaccine therapy and introduced tumor cell bank in a homepage (http://www.tumor.med.kyushu-u.ac.jp/).5. Possibility of cell-free vaccine therapy using GMP-grade exosomes secreted from tumor cells registered to tumor cell bank was indicated.