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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...

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Autores principales: Kitahara, Masaaki, Mizukoshi, Eishiro, Terashima, Takeshi, Nakagawa, Hidetoshi, Horii, Rika, Iida, Noriho, Arai, Kuniaki, Yamashita, Taro, Sakai, Yoshio, Yamashita, Tatsuya, Honda, Masao, Nakamoto, Yasunari, Kaneko, Shuichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226894/
https://www.ncbi.nlm.nih.gov/pubmed/32413834
http://dx.doi.org/10.1016/j.tranon.2020.100777
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author Kitahara, Masaaki
Mizukoshi, Eishiro
Terashima, Takeshi
Nakagawa, Hidetoshi
Horii, Rika
Iida, Noriho
Arai, Kuniaki
Yamashita, Taro
Sakai, Yoshio
Yamashita, Tatsuya
Honda, Masao
Nakamoto, Yasunari
Kaneko, Shuichi
author_facet Kitahara, Masaaki
Mizukoshi, Eishiro
Terashima, Takeshi
Nakagawa, Hidetoshi
Horii, Rika
Iida, Noriho
Arai, Kuniaki
Yamashita, Taro
Sakai, Yoshio
Yamashita, Tatsuya
Honda, Masao
Nakamoto, Yasunari
Kaneko, Shuichi
author_sort Kitahara, Masaaki
collection PubMed
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).
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spelling pubmed-72268942020-05-18 Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency Ablation Kitahara, Masaaki Mizukoshi, Eishiro Terashima, Takeshi Nakagawa, Hidetoshi Horii, Rika Iida, Noriho Arai, Kuniaki Yamashita, Taro Sakai, Yoshio Yamashita, Tatsuya Honda, Masao Nakamoto, Yasunari Kaneko, Shuichi Transl Oncol Original article 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). Neoplasia Press 2020-05-12 /pmc/articles/PMC7226894/ /pubmed/32413834 http://dx.doi.org/10.1016/j.tranon.2020.100777 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Kitahara, Masaaki
Mizukoshi, Eishiro
Terashima, Takeshi
Nakagawa, Hidetoshi
Horii, Rika
Iida, Noriho
Arai, Kuniaki
Yamashita, Taro
Sakai, Yoshio
Yamashita, Tatsuya
Honda, Masao
Nakamoto, Yasunari
Kaneko, Shuichi
Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency Ablation
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
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226894/
https://www.ncbi.nlm.nih.gov/pubmed/32413834
http://dx.doi.org/10.1016/j.tranon.2020.100777
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