Matsumoto Akihiko, Haraguchi Kyoko, Takahashi Tsuyoshi, Azuma Takeshi, Kanda Yoshinobu, Tomita Kyoichi, Kurokawa Mineo, Ogawa Seishi, Takahashi Koki, Chiba Shigeru, Kitamura Tadaichi
Department of Urology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Int J Urol. 2007 Apr;14(4):277-83. doi: 10.1111/j.1442-2042.2006.01723.x.
We performed a clinical trial of immunotherapy using autologous mature dendritic cells (DC) pulsed with autologous tumor lysate, for patients with metastatic renal cell carcinoma (RCC).
Patients with refractory metastatic RCC were enrolled in the study. All of them received interferon (IFN)-alpha treatment after nephrectomy and were followed over 3 months prior to this study. Autologous monocyte-derived immature DC were pulsed with lysate from autologous primary tumor as the antigen and keyhole limpet hemocyanin (KLH) as immunomodulator, and cultured in the presence of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and prostaglandin (PG)E2 to generate mature DC. Mature DC were injected intradermally near bilateral inguinal lymph nodes of the patients. A delayed-type hypersensitivity (DTH) test and enzyme-linked immunospot (ELISPOT) assay were performed to evaluate the immunological response. After 4 months from first injection, the clinical effect was evaluated by diagnostic imaging.
The treatments were well tolerated without significant toxicity by the patients who were an average of 65.7 years old and had multiple metastases in the lung and other organs. One of the two patients developed a positive DTH reaction to tumor lysate and the other patient only to KLH. The patient with a positive DTH reaction to tumor lysate had stable disease in the clinical evaluation.
We confirmed the safety of DC therapy in this clinical trial. The DTH test revealed that the DC therapy induced immunological response to RCC. On the other hand, it was necessary to reconsider the patient selection criteria.
我们对转移性肾细胞癌（RCC）患者进行了一项使用自体肿瘤裂解物脉冲处理的自体成熟树突状细胞（DC）的免疫治疗临床试验。
难治性转移性RCC患者被纳入该研究。他们均在肾切除术后接受了α干扰素（IFN）治疗，并在本研究前随访了3个月。将来自自体原发性肿瘤的裂解物作为抗原、匙孔血蓝蛋白（KLH）作为免疫调节剂，脉冲处理自体单核细胞衍生的未成熟DC，并在肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和前列腺素（PG）E2存在的情况下进行培养以生成成熟DC。将成熟DC皮内注射到患者双侧腹股沟淋巴结附近。进行迟发型超敏反应（DTH）试验和酶联免疫斑点（ELISPOT）测定以评估免疫反应。首次注射后4个月，通过诊断成像评估临床效果。
平均年龄为65.7岁、在肺部和其他器官有多处转移的患者对治疗耐受性良好，无明显毒性。两名患者中的一名对肿瘤裂解物产生了阳性DTH反应，另一名患者仅对KLH产生阳性反应。对肿瘤裂解物有阳性DTH反应的患者在临床评估中病情稳定。
我们在该临床试验中证实了DC治疗的安全性。DTH试验显示DC治疗诱导了对RCC的免疫反应。另一方面，有必要重新考虑患者选择标准。
