Gitlitz Barbara J, Belldegrun Arie S, Zisman Amnon, Chao Debby H, Pantuck Allan J, Hinkel Andreas, Mulders Peter, Moldawer Nancy, Tso Cho-Lea, Figlin Robert A
Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at University of California, Los Angeles, 10945 Le Conte Avenue, Suite 2333, Los Angeles, CA 90095, USA.
J Immunother. 2003 Sep-Oct;26(5):412-9. doi: 10.1097/00002371-200309000-00004.
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.
体外实验已证明，负载培养肿瘤裂解物的树突状细胞（TuLy-DC）可刺激强大的免疫调节作用并产生显著的抗肿瘤反应。我们报告了一项针对转移性肾细胞癌（mRCC）患者的TuLy-DC疫苗试点试验结果。14例mRCC患者接受了肾切除术以获取自体TuLy，其通过使肿瘤细胞经历3次冻融循环制备而成。树突状细胞由在GM-CSF、IL-4和10%自体血清存在的情况下培养的外周血CD14+前体细胞生成。患者先单独接受一次TuLy疫苗接种作为免疫对照，随后每周一次在腋窝中部皮内注射DC-TuLy，共接种3次。在每周接种疫苗前后收集外周血淋巴细胞，并评估其表型、细胞毒性和细胞因子谱的变化。TuLy-DC疫苗成功制备并给予了12例患者，而2例患者因术后身体状况下降未接受疫苗治疗。疫苗耐受性良好，仅记录到1级毒性。1例患者对治疗有部分反应，但这与免疫谱的任何显著变化均不对应。这项试点试验证明了为mRCC患者可靠制备基于树突状细胞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在体内持续介导抗肿瘤免疫反应的最有效治疗方案。
