Evidence map›Paper›PMID 29293510›Full record

ArticlePloS one2018

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 and 3 more

Open access · goldAbstract readClinical Trial, Phase I
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.7field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Yasuki HijikataDepartment of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Fukuoka, Japan.
Toshihiko OkazakiARO Advanced Medical Center, Kyushu University Hospital, Fukuoka, Japan.
Yoshihiro TanakaARO Advanced Medical Center, Kyushu University Hospital, Fukuoka, Japan.
Mutsunori MurahashiDepartment of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Fukuoka, Japan.
Yuichi YamadaDepartment of Anatomic Pathology, Pathological Sciences, Kyushu University, Fukuoka, Japan.
Kazunari YamadaDepartment of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Fukuoka, Japan.
Atsushi TakahashiDepartment of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Fukuoka, Japan.
Hiroyuki InoueDepartment of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Fukuoka, Japan.
Junji KishimotoARO Advanced Medical Center, Kyushu University Hospital, Fukuoka, Japan.
Yoichi NakanishiResearch Institute of Diseases of Chest, Kyushu University, Fukuoka, Japan.
Yoshinao OdaDepartment of Anatomic Pathology, Pathological Sciences, Kyushu University, Fukuoka, Japan.
Yusuke NakamuraHuman genome center, Institute of medical science, University of Tokyo, Tokyo, Japan.
Kenzaburo TaniDepartment of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Fukuoka, Japan.ORCID 0000-0003-3335-6188
Kyushu University Hospital · JPKyushu University · JPThe University of Tokyo · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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*02:01-positive and exhibiting high RNF43 expression in their tumor cells. They were administered 300 mg/m2 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.

Indexed as

ImmunotherapyAdultAgedAntineoplastic Agents, AlkylatingCombined Modality TherapyCyclophosphamideDNA-Binding ProteinsDose-Response Relationship, DrugFeasibility StudiesFemaleHumansImmunophenotypingMaleMiddle AgedNeoplasmsOncogene ProteinsAntineoplastic Agents, AlkylatingCyclophosphamideDNA-Binding ProteinsOncogene ProteinsPeptidesRNF43 protein, humanUbiquitin-Protein Ligases

Identifiers

PMID29293510
PMCPMC5749706
OpenAlexW2782199253

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.