Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency Ablation

被引:23
作者
Kitahara, Masaaki [1 ]
Mizukoshi, Eishiro [1 ]
Terashima, Takeshi [1 ]
Nakagawa, Hidetoshi [1 ]
Horii, Rika [1 ]
Iida, Noriho [1 ]
Arai, Kuniaki [1 ]
Yamashita, Taro [1 ]
Sakai, Yoshio [1 ]
Yamashita, Tatsuya [1 ]
Honda, Masao [1 ]
Nakamoto, Yasunari [2 ]
Kaneko, Shuichi [1 ]
机构
[1] Kanazawa Univ, Grad Sch Med, Dept Gastroenterol, Kanazawa, Ishikawa 9208641, Japan
[2] Univ Fukui, Fac Med Sci, Dept Internal Med 2, Fukui, Japan
基金
日本学术振兴会;
关键词
PERIPHERAL-BLOOD; RECURRENCE; CANCER; IMMUNOTHERAPY; RESPONSES; ADJUVANT; SURVIVAL; DISEASE; INNATE;
D O I
10.1016/j.tranon.2020.100777
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Dendritic cell (DC)-based immunotherapies are believed to help eradicate residual tumor cells, including hepatocellular car-cinoma (HCC). Here, we assessed the safety and clinical response to OK432-stimulated monocyte-derived DCs (MoDCs) in treating HCC after radiofrequency ablation (RFA). MoDCs were derived from 30 HCC patients in the presence of interleukin-4 and granulocyte-macrophage colony stimulating factor for 5 days and then cultured for 2 more days in the medium (basic protocol) or stimulated with OK432. On day 7, DCs were harvested and percutaneously injected into HCC tumors after RFA. We observed no grade 3 or 4 National Cancer Institute Common Toxicity Criteria adverse events. Kaplan-Meier analysis in-dicated that patients treated with RFA + OK432-stimulated DCs transfer had longer recurrence-free survival than those treated with RFA + basic-protocol DCs (median: 24.8 vs 13.0 months; P = .003). RFA with DC infusion can enhance var-ious tumor-associated antigen (TAA)-speci fic T-cell responses. Additionally, the 5-year RFS rate for patients with signi fi-cantly increased TAA-speci fic T-cell responses was much higher than for other patients (50.0% vs. 7.7%; P = .030). Our study provides useful information for development of HCC immunotherapies (trial registration: UMIN000001701).
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页数:6
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