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[用淋巴因子激活的杀伤细胞(LAK细胞)和白细胞介素-2对转移性肾细胞癌进行过继性免疫治疗的研究。II. 临床评估]

[Study of adoptive immunotherapy for metastatic renal cell carcinoma with lymphokine-activated killer (LAK) cells and interleukin-2. II. Clinical evaluation].

作者信息

Nomura K, Fujioka T

机构信息

Department of Urology, Iwate Medical University School of Medicine.

出版信息

Nihon Hinyokika Gakkai Zasshi. 1993 May;84(5):831-40. doi: 10.5980/jpnjurol1989.84.831.

Abstract

We evaluated adoptive immunotherapy using LAK cells combined with systemic administration of interleukin-2 (IL-2) in 11 patients with metastatic renal cell carcinoma. The LAK cells were generated by incubation in serum-free medium (AIM-V) supplemented with IL-2 (1,000 U/ml) for 4 days and were generally administered twice weekly (4 times/cycle). Daily administration of IL-2 (50 x 10(5) U) was started 3 days prior to the first LAK infusion and continued throughout the cycle. Each course of therapy comprised 1-6 cycles, with the total dose of LAK cells and IL-2 varying from 3.3-52.6 x 10(9) cells and 140-900 x 10(5) U, respectively. Clinical response was evaluated in terms of metastasis to specific organs (lung only: eight cases, lung and brain: one, lung and lymph nodes: one, lung and bone and pleuropericardium: one). The outcome was complete response in one patient, partial response in one, no change in six and disease progression in three. The response rate was 18.8%. This therapy was most effective against pulmonary metastases. Adverse reactions to LAK cell infusion included fever, headache, and chills. Eosinophilia and weight gain due to IL-2 administration were also observed. However, all of these symptoms were transient and no serious side effects occurred. In these patients, the proportion of natural killer (NK) cells (CD16) and cells with IL-2 receptor (CD25) among PBL was increased markedly in the early phase of therapy, and activated T cell (CD3+DR+) and suppressor T cells (CD8+11+) increased significantly at a later phase. It was suggested that the clinical response would be expected in case of increasing of CD16 cells or CD25 cells and augmentation of NK or LAK activity. Our results indicate that this regimen of adoptive immunotherapy shows some promise for the treatment of advanced renal cell carcinoma.

摘要

我们评估了采用淋巴因子激活的杀伤细胞(LAK细胞)联合全身应用白细胞介素-2(IL-2)对11例转移性肾细胞癌患者进行过继性免疫治疗的效果。LAK细胞在添加有IL-2(1000 U/ml)的无血清培养基(AIM-V)中培养4天生成,通常每周给药两次(每个周期4次)。在首次输注LAK细胞前3天开始每日给予IL-2(50×10⁵ U),并持续整个周期。每个疗程包括1 - 6个周期,LAK细胞和IL-2的总剂量分别为3.3 - 52.6×10⁹个细胞和140 - 900×10⁵ U。根据转移至特定器官的情况评估临床反应(仅肺转移:8例,肺和脑转移:1例,肺和淋巴结转移:1例,肺、骨和胸膜心包转移:1例)。结果为1例患者完全缓解,1例部分缓解,6例无变化,3例疾病进展。缓解率为18.8%。该疗法对肺转移最为有效。输注LAK细胞的不良反应包括发热、头痛和寒战。还观察到因给予IL-2导致的嗜酸性粒细胞增多和体重增加。然而,所有这些症状都是短暂的,未出现严重副作用。在这些患者中,治疗早期外周血淋巴细胞(PBL)中自然杀伤(NK)细胞(CD16)和具有IL-2受体的细胞(CD25)的比例显著增加,后期活化T细胞(CD3⁺DR⁺)和抑制性T细胞(CD8⁺11⁺)显著增加。提示CD16细胞或CD25细胞增加以及NK或LAK活性增强时可能出现临床反应。我们的结果表明,这种过继性免疫治疗方案对晚期肾细胞癌的治疗显示出一定的前景。

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