Kan N, Okino T, Nakanishi M, Satou K, Mise K, Ohgaki K, Hori T, Kodama H, Tobe T
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Hum Cell. 1988 Sep;1(3):289-96.
Our method of adoptive immunotherapy (AIT) using autologous IL-2-cultured lymphocytes differs from so-called LAK therapy in several points. We (1) obtain cultured lymphocytes from effusion lymphocytes (EL) or regional lymph-node lymphocytes (RLNL), when possible, rather than peripheral blood lymphocytes (PBL), (2) use crude IL-2 to induce T cell proliferation and to maintain killer activity, (3) use sonicated autologous tumor extract as antigen (Ag) to stimulate proliferation of cytotoxic T cells, and (4) pretreat the patients with local administration of OK-432 before AIT to induce effector cells that act synergistically with transferred killer cells. Surface marker analysis showed that OKT3, IL-2 receptor, Leu 2+15- cells were elevated while Leu 11a and Leu 3+8+ cells were decreased. Culture of RLNL augmented the expression of Leu 3+8- marker. Both of PBL and RLNL responded to Ag, and their auto-tumor killing activities were augmented in about half of the patients while rarely decrease by the addition of Ag. Response rates of patients with pleural effusion due to breast cancer and those with liver metastasis of breast cancer were 94% and 60%, respectively. Moreover, the survival was prolonged in the treated patients with pleural effusion or gastric cancer patients with peritoneal dissemination.
我们采用自体白细胞介素-2培养淋巴细胞进行过继性免疫疗法(AIT)的方法在几个方面与所谓的淋巴因子激活的杀伤细胞(LAK)疗法有所不同。我们(1)尽可能从积液淋巴细胞(EL)或区域淋巴结淋巴细胞(RLNL)而非外周血淋巴细胞(PBL)中获取培养的淋巴细胞,(2)使用粗制白细胞介素-2诱导T细胞增殖并维持杀伤活性,(3)使用经超声处理的自体肿瘤提取物作为抗原(Ag)刺激细胞毒性T细胞增殖,以及(4)在AIT前对患者进行局部注射OK-432预处理,以诱导与转移的杀伤细胞协同作用的效应细胞。表面标志物分析显示,OKT3、白细胞介素-2受体、Leu 2 + 15 -细胞升高,而Leu 11a和Leu 3 + 8 +细胞减少。RLNL的培养增强了Leu 3 + 8 -标志物的表达。PBL和RLNL对Ag均有反应,并且在约一半的患者中它们的自身肿瘤杀伤活性增强,而加入Ag后很少降低。乳腺癌伴胸腔积液患者和乳腺癌肝转移患者的缓解率分别为94%和60%。此外,胸腔积液治疗患者或胃癌伴腹膜播散患者的生存期延长。