A phase I clinical trial of RNF43 peptide-related immune cell therapy combined with low-dose cyclophosphamide in patients with advanced solid tumors

Yasuki Hijikata, Toshihiko Okazaki, Yoshihiro Tanaka, Mutsunori Murahashi, Yuichi Yamada, Kazunari Yamada, Atsushi Takahashi, Hiroyuki Inoue, Junji Kishimoto, Yoichi Nakanishi, Yoshinao Oda, Yusuke Nakamura, Kenzaburo Tani

研究成果: ジャーナルへの寄稿記事

3 引用 (Scopus)

抄録

The objective of this study was to investigate the safety and the tolerability of combined cellular immunotherapy with low-dose cyclophosphamide (CPA) in patients with advanced solid tumors. This study targeted a novel tumor-associated antigen, ring finger protein 43 (RNF43). Eligible patients were resistant to standard therapy, HLA-A*24:02- or A*02:01positive and exhibiting high RNF43 expression in their tumor cells. They were administered 300 mg/m 2 CPA followed by autologous lymphocytes, preliminarily cultured with autologous RNF43 peptide-pulsed dendritic cells (DCs), RNF43 peptide-pulsed DCs and systemic low dose interleukin-2. The primary endpoint was safety whereas the secondary endpoint was immunological and clinical response to treatment. Ten patients, in total, were enrolled in this trial. Primarily, no adverse events greater than Grade 3 were observed. Six out of 10 patients showed stable disease (SD) on day 49, while 4 other patients showed progressive disease. In addition, one patient with SD exhibited a partial response after the second trial. The frequency of regulatory T cells (Tregs) in patients with SD significantly decreased after CPA administration. The ratio of interferon-γ-producing, tumor-reactive CD8 + T cells increased with time in patients with SD. We successfully showed that the combination of immune cell therapy and CPA was safe, might induce tumor-specific immune responses and clinical efficacy, and was accompanied by a decreased ratio of Tregs in patients with RNF43-positive advanced solid tumors.

元の言語英語
記事番号e0187878
ジャーナルPloS one
13
発行部数1
DOI
出版物ステータス出版済み - 1 1 2018

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Clinical Trials, Phase I
cyclophosphamide
Cell- and Tissue-Based Therapy
Cyclophosphamide
Fingers
Tumors
clinical trials
peptides
therapeutics
Peptides
neoplasms
dosage
Neoplasms
Proteins
T-cells
proteins
cells
dendritic cells
endpoints
Dendritic Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

これを引用

A phase I clinical trial of RNF43 peptide-related immune cell therapy combined with low-dose cyclophosphamide in patients with advanced solid tumors. / Hijikata, Yasuki; Okazaki, Toshihiko; Tanaka, Yoshihiro; Murahashi, Mutsunori; Yamada, Yuichi; Yamada, Kazunari; Takahashi, Atsushi; Inoue, Hiroyuki; Kishimoto, Junji; Nakanishi, Yoichi; Oda, Yoshinao; Nakamura, Yusuke; Tani, Kenzaburo.

:: PloS one, 巻 13, 番号 1, e0187878, 01.01.2018.

研究成果: ジャーナルへの寄稿記事

Hijikata, Yasuki ; Okazaki, Toshihiko ; Tanaka, Yoshihiro ; Murahashi, Mutsunori ; Yamada, Yuichi ; Yamada, Kazunari ; Takahashi, Atsushi ; Inoue, Hiroyuki ; Kishimoto, Junji ; Nakanishi, Yoichi ; Oda, Yoshinao ; Nakamura, Yusuke ; Tani, Kenzaburo. / A phase I clinical trial of RNF43 peptide-related immune cell therapy combined with low-dose cyclophosphamide in patients with advanced solid tumors. :: PloS one. 2018 ; 巻 13, 番号 1.
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abstract = "The objective of this study was to investigate the safety and the tolerability of combined cellular immunotherapy with low-dose cyclophosphamide (CPA) in patients with advanced solid tumors. This study targeted a novel tumor-associated antigen, ring finger protein 43 (RNF43). Eligible patients were resistant to standard therapy, HLA-A*24:02- or A*02:01positive and exhibiting high RNF43 expression in their tumor cells. They were administered 300 mg/m 2 CPA followed by autologous lymphocytes, preliminarily cultured with autologous RNF43 peptide-pulsed dendritic cells (DCs), RNF43 peptide-pulsed DCs and systemic low dose interleukin-2. The primary endpoint was safety whereas the secondary endpoint was immunological and clinical response to treatment. Ten patients, in total, were enrolled in this trial. Primarily, no adverse events greater than Grade 3 were observed. Six out of 10 patients showed stable disease (SD) on day 49, while 4 other patients showed progressive disease. In addition, one patient with SD exhibited a partial response after the second trial. The frequency of regulatory T cells (Tregs) in patients with SD significantly decreased after CPA administration. The ratio of interferon-γ-producing, tumor-reactive CD8 + T cells increased with time in patients with SD. We successfully showed that the combination of immune cell therapy and CPA was safe, might induce tumor-specific immune responses and clinical efficacy, and was accompanied by a decreased ratio of Tregs in patients with RNF43-positive advanced solid tumors.",
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AU - Tanaka, Yoshihiro

AU - Murahashi, Mutsunori

AU - Yamada, Yuichi

AU - Yamada, Kazunari

AU - Takahashi, Atsushi

AU - Inoue, Hiroyuki

AU - Kishimoto, Junji

AU - Nakanishi, Yoichi

AU - Oda, Yoshinao

AU - Nakamura, Yusuke

AU - Tani, Kenzaburo

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