Höltl Lorenz, Zelle-Rieser Claudia, Gander Hubert, Papesh Christine, Ramoner Reinhold, Bartsch Georg, Rogatsch Hermann, Barsoum Adel L, Coggin Joseph H, Thurnher Martin
Department of Urology, University of Innsbruck, 6020 Innsbruck, Austria.
Clin Cancer Res. 2002 Nov;8(11):3369-76.
We wanted to evaluate feasibility and safety of dendritic cell-based immunotherapy in patients with metastatic renal cell carcinoma (RCC).
Patients with metastatic RCC (n = 35) received vaccinations (i.v. or i.d.) of CD83+ autologous monocyte-derived dendritic cells (moDCs). MoDCs were loaded with lysate of cultured autologous or allogeneic permanent tumor cells (A-498) as well as keyhole limpet hemocyanin as control and helper antigen. Maturation of moDCs was induced by a combination of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and prostaglandin E2.
Treatment was associated with transient flu-like symptoms. In 2 of 27 evaluable patients, any evidence of disease disappeared (complete response). In both cases, metastatic tissue had been the source of tumor antigen. One patient had an objective partial response. Seven patients had stable disease, the remaining 17 patients had progressive disease. In 11 of 11 patients evaluated, moDCs induced strong immune responses against keyhole limpet hemocyanin. In 5 of 6 patients tested, enhanced immune responses against oncofetal antigen (immature laminin receptor; OFA/LRP) could also be detected. The strongest responses against OFA/LRP were detectable in 2 patients with complete response and partial response, respectively. At the time of submission, mean follow up is 32 months and 8 patients are currently alive.
Our data indicate that moDC-based vaccination is well tolerated and has immunological as well as clinical effects in patients with metastatic RCC. OFA/LRP might be an attractive candidate antigen for DC-based immunotherapy of RCC.
我们旨在评估基于树突状细胞的免疫疗法在转移性肾细胞癌（RCC）患者中的可行性和安全性。
转移性RCC患者（n = 35）接受了CD83 + 自体单核细胞衍生树突状细胞（moDCs）的疫苗接种（静脉内或皮内）。moDCs负载有培养的自体或同种异体永久性肿瘤细胞（A - 498）的裂解物以及作为对照和辅助抗原的钥孔戚血蓝蛋白。通过肿瘤坏死因子α、白细胞介素1β、白细胞介素6和前列腺素E2的组合诱导moDCs成熟。
治疗与短暂的流感样症状相关。在27例可评估患者中的2例中，疾病的任何证据均消失（完全缓解）。在这两种情况下，转移组织均为肿瘤抗原的来源。1例患者出现客观部分缓解。7例患者疾病稳定，其余17例患者疾病进展。在11例评估患者中的11例中，moDCs诱导了针对钥孔戚血蓝蛋白的强烈免疫反应。在6例测试患者中的5例中，还可检测到针对癌胚抗原（未成熟层粘连蛋白受体；OFA/LRP）的增强免疫反应。分别在2例完全缓解和部分缓解的患者中可检测到针对OFA/LRP的最强反应。在提交本文时，平均随访时间为32个月，目前有8例患者存活。
我们的数据表明，基于moDC的疫苗接种耐受性良好，对转移性RCC患者具有免疫和临床效果。OFA/LRP可能是基于DC的RCC免疫疗法的有吸引力的候选抗原。
