A pilot trial of tumor lysate-loaded dendritic cells for the treatment of metastatic renal cell carcinoma
A pilot trial of tumor lysate-loaded dendritic cells for the treatment of metastatic renal cell carcinoma
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DOI：
10.1097/00002371-200309000-00004
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发表时间：
2003-09-01
影响因子：
3.9
通讯作者：
Figlin, RA
中科院分区：
文献类型：
--
作者：
Gitlitz, BJ;Belldegrun, AS;Figlin, RA
体外培养的负载肿瘤裂解物的树突状细胞 (TuLy-DC) 已被证明可以刺激有效的免疫调节并产生显着的抗肿瘤反应。我们报告了 TuLy-DC 疫苗针对转移性肾细胞癌 (mRCC) 患者的初步试验结果。 14 名 mRCC 患者接受肾切除术，以获得通过将肿瘤细胞进行 3 次冻融循环制备的自体 TuLy。树突状细胞由在 GM-CSF、IL-4 和 10% 自体血清存在下培养的外周血 CD14(+) 前体产生。患者仅接受 1 次 TuLy 疫苗接种作为免疫对照，随后每周 3 次在腋中区皮内注射 DC-TuLy 疫苗接种。每周接种疫苗之前和之后收集外周血淋巴细胞，并评估表型、细胞毒性和细胞因子谱的变化。 TuLy-DC疫苗已成功制备并给12名患者注射，而2名患者因术后体力状态下降而没有接受疫苗治疗。这些疫苗耐受性良好，仅发现 1 级毒性。一名患者对治疗有部分反应，但与免疫学特征没有任何显着变化相对应。该试点试验证明了为 mRCC 患者可靠制备基于 DC 的疫苗的安全性和可行性。我们的数据表明自体 TuLy-DC 疫苗仅产生有限的临床反应。需要进一步的临床研究来确定能够持续介导体内抗肿瘤免疫反应的最有效的治疗方案。
Cultured tumor lysate-loaded dendritic cells (TuLy-DC) have been demonstrated in vitro to stimulate potent immune modulations and generate significant antitumor response. We report the results of a pilot trial of TuLy-DC vaccine for patients with metastatic renal cell carcinoma (mRCC). Fourteen mRCC patients underwent nephrectomy to obtain autologous TuLy prepared by subjecting tumor cells to 3 freeze/thaw cycles. Dendritic cells were generated from peripheral blood CD14(+) precursors cultured in the presence of GM-CSF, IL-4, and 10% autologous serum. Patients received one vaccination of TuLy alone as an immunologic control, followed by 3 weekly vaccinations of DC-TuLy injected intradermally in the midaxillary region. Peripheral blood lymphocytes were collected before and after weekly vaccines and were assessed for changes in phenotype, cytotoxicity, and cytokine profile. The TuLy-DC vaccine was successfully prepared and administered to 12 patients, whereas 2 patients did not receive vaccine treatment due to declines in postoperative performance status. The vaccines were well tolerated, with only grade 1 toxicities noted. One patient had a partial response to treatment that did not correspond to any significant change in immunologic profile. This pilot trial demonstrated both the safety and feasibility of reliably preparing a DC-based vaccine for mRCC patients. Our data suggest that autologous TuLy-DC vaccines generate only limited clinical response. Further clinical studies are needed to identify the most potent treatment regimen that can consistently mediate an antitumor immune response in vivo.