Ikawa T, Eura M, Fukiage T, Murakami H, Yamasaki S, Fukuda K, Fukushima M, Arishima S, Maehara T, Ishikawa T
Dept. of Otorhinolaryngology, Kumamoto University School of Medicine.
Gan To Kagaku Ryoho. 1989 Apr;16(4 Pt 2-2):1438-47.
For clinical application of adoptive immunotherapy, it is necessary to prepare a sufficient number of autologous tumor specific effector cells. A large amount of peripheral blood lymphocytes was obtained by leukapheresis using a Heamonetics V50 pheresis system. Autologous tumor- and lymphokine-activated killer (ATLAK) cells were induced by autologous mixed lymphocyte tumor cell culture (autologous MLTC) and further activation with recombinant interleukin-2 (rIL-2). Another problem was the difficulty of obtaining a sufficient number of highly activated effector cells to reach the target tumor tissue. Direct infusion of effector cells into a feeding artery was effective for cell accumulation in the target. ATLAK cells were infused into maxillary artery in 4 patients with maxillary squamous cell carcinoma. The results indicated that the therapy was effective for reduction of the tumor mass. After immunotherapy, surgery was performed and the tissues were histologically examined. Degenerated tumor cells and intensive infiltration by mononuclear cells and macrophages were seen in the surrounding fibrous tissue. However, the quantity of fresh autologous tumor cells available from open biopsy was limited. Allogeneic cultured tumor cell line was used as stimulator of lymphocytes instead of autologous tumor cells. The killing activity of the allogeneic tumor and lymphokine activated killer (Allo-TLAK) cells was significantly induced against the autologous tumor cells. Antitumor effect was observed in 5 out of 9 patients. Side effects were minor, such as slight fever and blood eosinophilia, which may be due to the rIL-2 function. These results indicate that this method of therapy is an effective form of adoptive immunotherapy.
对于过继性免疫疗法的临床应用，制备足够数量的自体肿瘤特异性效应细胞是必要的。使用血细胞分离机（Heamonetics V50血细胞分离系统）通过白细胞单采术获取大量外周血淋巴细胞。通过自体混合淋巴细胞肿瘤细胞培养（自体MLTC）并进一步用重组白细胞介素-2（rIL-2）激活来诱导自体肿瘤和淋巴因子激活的杀伤细胞（ATLAK细胞）。另一个问题是难以获得足够数量的高度激活的效应细胞以到达靶肿瘤组织。将效应细胞直接注入供血动脉对细胞在靶部位的聚集是有效的。将ATLAK细胞注入4例上颌鳞状细胞癌患者的上颌动脉。结果表明该疗法对肿瘤肿块的缩小有效。免疫治疗后，进行手术并对组织进行组织学检查。在周围纤维组织中可见变性的肿瘤细胞以及单核细胞和巨噬细胞的密集浸润。然而，开放活检可获得的新鲜自体肿瘤细胞数量有限。使用同种异体培养的肿瘤细胞系代替自体肿瘤细胞作为淋巴细胞的刺激物。同种异体肿瘤和淋巴因子激活的杀伤细胞（Allo-TLAK细胞）对自体肿瘤细胞的杀伤活性被显著诱导。9例患者中有5例观察到抗肿瘤作用。副作用较小，如低热和血液嗜酸性粒细胞增多，这可能归因于rIL-2的作用。这些结果表明这种治疗方法是过继性免疫疗法的一种有效形式。
