Rizell Magnus, Sternby Eilard Malin, Andersson Mats, Andersson Bengt, Karlsson-Parra Alex, Suenaert Peter
Transplantation Center, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Front Oncol. 2019 Jan 21;9:19. doi: 10.3389/fonc.2019.00019. eCollection 2019.
Several lines of evidence support immunotherapy in hepatocellular carcinoma (HCC). We have shown that intratumoral injections of the immune primer ilixadencel (pro-inflammatory allogeneic dendritic cells) are safe in renal-cell carcinoma. Here, we assessed ilixadencel as a single agent and combined with sorafenib in advanced HCC. Of 17 HCC patients enrolled, 12 patients received ilixadencel at the dose of 10 × 10 cells (six as monotherapy and six in combination with sorafenib), and five received ilixadencel at the dose of 20 × 10 cells as monotherapy. The primary objective was to evaluate tolerability. All patients had at least one adverse event, with 30% of such events considered as treatment-related, with one single treatment-related grade three event. The most common toxicity was grade 1 and 2 fever and chills. Eleven of 15 evaluable patients (73%) showed increased frequency of tumor-specific CD8 T cells in peripheral blood. Overall one patient had a partial response (with ilixadencel as monotherapy), and five had stable disease as overall best response per mRECIST. The median time to progression was 5.5 months, and overall survival ranged from 1.6 to 21.4 months. Our study confirms the safety of ilixadencel as single agent or in combination with sorafenib and indicates tumor-specific immunological responses in advanced HCC. www.ClinicalTrials.gov, identifier: NCT01974661.
多项证据支持免疫疗法用于肝细胞癌（HCC）的治疗。我们已表明，瘤内注射免疫启动剂伊立替康（促炎性同种异体树突状细胞）在肾细胞癌中是安全的。在此，我们评估了伊立替康作为单一药物以及与索拉非尼联合用于晚期HCC的情况。在纳入的17例HCC患者中，12例患者接受了剂量为10×10细胞的伊立替康治疗（6例为单药治疗，6例与索拉非尼联合治疗），5例患者接受了剂量为20×10细胞的伊立替康单药治疗。主要目的是评估耐受性。所有患者至少发生了一次不良事件，其中30%的此类事件被认为与治疗相关，仅有一例与治疗相关的3级事件。最常见的毒性是1级和2级发热及寒战。15例可评估患者中的11例（73%）外周血中肿瘤特异性CD8 T细胞频率增加。总体而言，1例患者出现部分缓解（伊立替康单药治疗），5例患者根据改良RECIST标准总体最佳反应为病情稳定。中位进展时间为5.5个月，总生存期为1.6至21.4个月。我们的研究证实了伊立替康作为单一药物或与索拉非尼联合使用的安全性，并表明晚期HCC中存在肿瘤特异性免疫反应。 临床试验.gov网站，标识符：NCT01974661。
