Evidence map›Paper›PMID 38367684›Full record

ArticleEuropean journal of pharmacology2024

Toxicology, pharmacokinetics, and immunogenicity studies of CCR4-IL2 bispecific immunotoxin in rats and minipigs.

Zhaohui Wang, Rashmi Ramakrishna, Yong Wang, Yue Qiu, Jihong Ma, Danielle Mintzlaff, Huiping Zhang, Bing Li, Benjamin Hammell, M Scott Lucia and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 38% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Immunogenicity evaluation of altSonflex1-2-3Frontiers in immunology · 2025
    Article
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

15 authors at 1 institution in 2 countries.

Zhaohui WangDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Rashmi RamakrishnaDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Yong WangDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Yue QiuDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110122, China.
Jihong MaDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Danielle MintzlaffDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Huiping ZhangDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Bing LiDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Benjamin HammellDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
M Scott LuciaDepartment of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Elizabeth PomfretDivision of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
An-Jey A SuDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Kia M WashingtonDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
David W MathesDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Zhirui WangDivision of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: zhirui.wang@cuanschutz.edu.
University of Colorado Anschutz Medical Campus · US

Funding

Colorado REACH HubU01HL152405 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI DUKE, RICHARD C · 2019 to 2022
$5.1M
CCR4-IL2 Bispecific Immunotoxin for Targeted Therapy of Cutaneous T-Cell LymphomaR42CA261547 · NCI · ROCK IMMUNE LLC · PI WANG, ZHIRUI · 2021 to 2025
$2.4M
NCI NIH HHS R42 CA261547NHLBI NIH HHS U01 HL152405
6 · The paper itself

Abstract

We have developed a diphtheria toxin-based recombinant human CCR4-IL2 bispecific immunotoxin (CCR4-IL2-IT) for targeted therapy of cutaneous T-cell lymphoma (CTCL). CCR4-IL2-IT demonstrated superior efficacy in an immunodeficient mouse CTCL model. Recently, we have compared the in vivo efficacy of CCR4-IL2-IT versus Brentuximab (FDA approved leading drug in CTCL market) in the same immunodeficient mouse CTCL model. The comparison demonstrated that CCR4-IL2-IT was significantly more effective than Brentuximab. In this study, we have performed non-GLP (Good Laboratory Practice) toxicology, pharmacokinetics, immunogenicity studies of CCR4-IL2-IT in both rats and minipigs. CCR4-IL2-IT demonstrated excellent safety profiles in both rats and minipigs. The maximum tolerated dose of CCR4-IL2-IT was determined as 0.4 mg/kg in both rats and minipigs. Complete blood count and chemistry analysis did not show significant difference for all measured parameters between the blood samples of pre-injection versus post-injection from the five-day toxicology studies of CCT4-IL2-IT in both rats and minipigs. Histology analysis did not show difference between the PBS treatment group versus CCR4-IL2-IT treatment group at 50 μg/kg in both rats and minipigs. The half-life of CCR4-IL2-IT was determined as about 45 min in rats and 30 min in minipigs. The antibodies against CCR4-IL2-IT were detected in about two weeks after CCR4-IL2-IT treatment. CCR4-IL2-IT did not induce cytokine release syndrome in a peripheral blood mononuclear cell derived humanized mouse model. The depletion of CCR4

Indexed as

Antineoplastic AgentsImmunotoxinsAnimalsAntibodies, MonoclonalHumansInterleukin-2Leukocytes, MononuclearMiceMice, SCIDRatsReceptors, CCR4SwineSwine, MiniatureAntibodies, MonoclonalAntineoplastic AgentsCCR4 protein, humanImmunotoxinsInterleukin-2Receptors, CCR4CCR4-IL2 bispecific immunotoxinCutaneous T cell lymphomaImmunotoxin pharmacokineticsToxicology study

Identifiers

PMID38367684
PMCPMC10939744
OpenAlexW4391849972

What OpenQuestion holds

Textmetadata
LicenceTDM
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Registered trials

None linked

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.