Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency Ablation
Dendritic cell (DC)–based immunotherapies are believed to help eradicate residual tumor cells, including hepatocellular carcinoma (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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-07-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523319305388 |
| _version_ | 1818514832872177664 |
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| author | Masaaki Kitahara Eishiro Mizukoshi Takeshi Terashima Hidetoshi Nakagawa Rika Horii Noriho Iida Kuniaki Arai Taro Yamashita Yoshio Sakai Tatsuya Yamashita Masao Honda Yasunari Nakamoto Shuichi Kaneko |
| author_facet | Masaaki Kitahara Eishiro Mizukoshi Takeshi Terashima Hidetoshi Nakagawa Rika Horii Noriho Iida Kuniaki Arai Taro Yamashita Yoshio Sakai Tatsuya Yamashita Masao Honda Yasunari Nakamoto Shuichi Kaneko |
| author_sort | Masaaki Kitahara |
| collection | DOAJ |
| description | Dendritic cell (DC)–based immunotherapies are believed to help eradicate residual tumor cells, including hepatocellular carcinoma (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 indicated 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 various tumor-associated antigen (TAA)–specific T-cell responses. Additionally, the 5-year RFS rate for patients with significantly increased TAA-specific 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). |
| first_indexed | 2024-12-11T00:21:08Z |
| format | Article |
| id | doaj.art-e4382fa13d69434cb46c6ab39de6689e |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-11T00:21:08Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-e4382fa13d69434cb46c6ab39de6689e2022-12-22T01:27:45ZengElsevierTranslational Oncology1936-52332020-07-01137100777Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency AblationMasaaki Kitahara0Eishiro Mizukoshi1Takeshi Terashima2Hidetoshi Nakagawa3Rika Horii4Noriho Iida5Kuniaki Arai6Taro Yamashita7Yoshio Sakai8Tatsuya Yamashita9Masao Honda10Yasunari Nakamoto11Shuichi Kaneko12Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, JapanDepartment of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan; Address all correspondence to: Eishiro Mizukoshi, MD, PhD, Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, JapanDepartment of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, JapanDepartment of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, JapanDepartment of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, JapanDepartment of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, JapanDepartment of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, JapanDepartment of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, JapanDepartment of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, JapanDepartment of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, JapanSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, JapanDepartment of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, JapanDendritic cell (DC)–based immunotherapies are believed to help eradicate residual tumor cells, including hepatocellular carcinoma (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 indicated 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 various tumor-associated antigen (TAA)–specific T-cell responses. Additionally, the 5-year RFS rate for patients with significantly increased TAA-specific 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).http://www.sciencedirect.com/science/article/pii/S1936523319305388 |
| spellingShingle | Masaaki Kitahara Eishiro Mizukoshi Takeshi Terashima Hidetoshi Nakagawa Rika Horii Noriho Iida Kuniaki Arai Taro Yamashita Yoshio Sakai Tatsuya Yamashita Masao Honda Yasunari Nakamoto Shuichi Kaneko Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency Ablation Translational Oncology |
| title | Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency Ablation |
| title_full | Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency Ablation |
| title_fullStr | Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency Ablation |
| title_full_unstemmed | Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency Ablation |
| title_short | Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency Ablation |
| title_sort | safety and long term outcome of intratumoral injection of ok432 stimulated dendritic cells for hepatocellular carcinomas after radiofrequency ablation |
| url | http://www.sciencedirect.com/science/article/pii/S1936523319305388 |
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