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[使用活化淋巴细胞的区域过继性免疫疗法]

[Regional adoptive immunotherapy using activated lymphocytes].

作者信息

Ebina T, Isono N, Murata K, Yokoyama J, Mikuni J, Ohuchi K

机构信息

Division of Immunology, Research Institute Miyagi Cancer Center.

出版信息

Gan To Kagaku Ryoho. 1996 Sep;23(11):1549-52.

PMID:8854802
Abstract

The antitumor effect of PSK was analysed with the "double grafted tumor system" in which BALB/c mice received simultaneous intradermal inoculations of Meth-A in the right (10(6) cells) and left (2 x 10(5) cells) flanks and were then injected with PSK in the right tumor on day 3. PSK inhibited the growth of not only the right but also the left, non-treated tumor. Immunized spleen cells were taken from mice which had been cured by intratumoral administration of 5 mg of PSK. On day 3, one hour after intravenous injection of cyclophosphamide, immunized spleen cells (2 x 10(7) cells/mouse) were injected into the Meth-A tumor. Adoptive transfer of PSK immunized spleen cells caused the complete regression of Meth-A tumors. However, the intravenous administration of spleen cells showed no antitumor effect. Expansion of peripheral blood lymphocytes was stimulated with immobilized anti CD3 antibody plus IL-2 for use in adoptive immunotherapy. gamma delta T cells proliferated in response to immobilized anti CD3. About 5 x 10(9) BRM-activated killer (BAK) cells were treated in cancer patients who gave their informed consent. One patient with colon cancer and metastatic cancer of the liver was treated with BAK cells by transcatheter arterial infusion without side effect. During the course of BAK treatment, serum IAP CIAE (crossed immunoaffino electrophoresis) pattern of patient changed tumor IAP pattern to normal IAP pattern. Two patients with malignant tumor in maxillary sinus were treated with BAK cells and OK-432 intratumorally. BAK treatment induced more infiltration of T cells, M phi and granulocytes in the tumor than OK-432 treatment alone and showed an antitumor effect with extensive necrosis.

摘要

采用“双移植瘤系统”分析了PSK的抗肿瘤作用,即BALB/c小鼠在右侧(10⁶个细胞)和左侧(2×10⁵个细胞)胁腹同时进行Meth-A皮内接种,然后在第3天对右侧肿瘤注射PSK。PSK不仅抑制了右侧肿瘤的生长,还抑制了左侧未处理肿瘤的生长。免疫脾细胞取自经瘤内注射5mg PSK治愈的小鼠。在第3天,静脉注射环磷酰胺1小时后,将免疫脾细胞(2×10⁷个细胞/小鼠)注射到Meth-A肿瘤中。PSK免疫脾细胞的过继转移导致Meth-A肿瘤完全消退。然而,静脉注射脾细胞未显示出抗肿瘤作用。用固定化抗CD3抗体加IL-2刺激外周血淋巴细胞扩增以用于过继免疫治疗。γδT细胞对固定化抗CD3有增殖反应。约5×10⁹个生物反应调节剂激活的杀伤(BAK)细胞用于治疗已签署知情同意书的癌症患者。一名患有结肠癌和肝转移癌的患者通过经导管动脉灌注接受BAK细胞治疗,无副作用。在BAK治疗过程中,患者的血清IAP CIAE(交叉免疫亲和电泳)图谱将肿瘤IAP图谱转变为正常IAP图谱。两名上颌窦恶性肿瘤患者瘤内注射BAK细胞和OK-432进行治疗。与单独使用OK-432治疗相比,BAK治疗诱导肿瘤内T细胞、Mφ和粒细胞浸润更多,并显示出具有广泛坏死的抗肿瘤作用。

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