Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells.
Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells.
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发表时间：
2003-05
期刊：
影响因子：
11.2
通讯作者：
Z. Su;J. Dannull;A. Heiser;Donna R. Yancey;S. Pruitt;J. Madden;Doris Coleman;D. Niedzwiecki;E. Gilboa;J. Vieweg
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作者：
Z. Su;J. Dannull;A. Heiser;Donna R. Yancey;S. Pruitt;J. Madden;Doris Coleman;D. Niedzwiecki;E. Gilboa;J. Vieweg
转染肾肿瘤总 RNA 的自体树突状细胞已被证明是体外 CTL 和抗肿瘤免疫的有效刺激剂。进行了一项 I 期试验，以评估该策略在转移性肾细胞癌受试者中诱导肿瘤特异性 T 细胞反应的可行性、安全性和有效性。肾肿瘤 RNA 转染的树突状细胞被给予 10 名可评估的研究患者，没有证据表明剂量限制性毒性或疫苗相关的副作用，包括自身免疫。七名可评估受试者中有六名在免疫后检测到肿瘤特异性 T 细胞的扩增。疫苗诱导的 T 细胞反应针对广泛的肾肿瘤相关抗原，包括端粒酶逆转录酶、G250 和癌胚抗原，但不针对正常肾组织表达的自身抗原。尽管大多数患者在接种疫苗后接受了二次治疗，但研究对象的肿瘤相关死亡率出乎意料地低，平均随访 19.8 个月后，10 名患者中只有 3 人死于疾病。这些数据为继续临床研究这种多价疫苗策略治疗转移性肾细胞癌以及可能的其他癌症提供了科学依据。
Autologous dendritic cells transfected with total renal tumor RNA have been shown to be potent stimulators of CTLs and antitumor immunity in vitro. A Phase I trial was conducted to evaluate this strategy for feasibility, safety, and efficacy to induce tumor-specific T-cell responses in subjects with metastatic renal cell carcinoma. Renal tumor RNA-transfected dendritic cells were administered to 10 evaluable study patients with no evidence of dose-limiting toxicity or vaccine-related adverse effects including autoimmunity. In six of seven evaluable subjects, expansion of tumor-specific T cells was detected after immunization. The vaccine-induced T-cell reactivities were directed against a broad set of renal tumor-associated antigens, including telomerase reverse transcriptase, G250, and oncofetal antigen, but not against self-antigens expressed by normal renal tissues. Although most patients underwent secondary therapies after vaccination, tumor-related mortality of the study subjects was unexpectedly low with only 3 of 10 patients dying from disease after a mean follow-up of 19.8 months. These data provide a scientific rationale for continued clinical investigation of this polyvalent vaccine strategy in the treatment of metastatic renal cell carcinoma and, potentially, other cancers.