Evidence map›Paper›PMID 28784559›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017

Adnectin-Based Design of Chimeric Antigen Receptor for T Cell Engineering.

Xiaolu Han, Gunce E Cinay, Yifan Zhao, Yunfei Guo, Xiaoyang Zhang, Pin Wang

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 5% 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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 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

6 authors at 1 institution in 1 country.

Xiaolu HanGenetic, Molecular, and Cellular Biology Program, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Gunce E CinayDepartment of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA.
Yifan ZhaoDepartment of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA.
Yunfei GuoDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Xiaoyang ZhangMork Family Department of Chemical Engineering and Materials Science, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA.
Pin WangDepartment of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA; Mork Family Department of Chemical Engineering and Materials Science, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: pinwang@usc.edu.
University of Southern California · US

Funding

Transduction of Hematopoietic Stem Cells for Enhanced Immunotherapy of MelanomaP01CA132681 · NCI · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI BALTIMORE, DAVID · 2010 to 2014
$14.4M
Targeting lentiviruses to infect chosen cellsR01AI068978 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI WANG, PIN · 2006 to 2010
$2.9M
In situ Redirection of T cell Specificity and Imaging of Targeted CAR Expression.R01EB017206 · NIBIB · TEL-AVIV SOURASKY MEDICAL CENTER · PI ESHHAR, ZELIG, NAJJAR, AMER M · 2013 to 2016
$1.8M
SUPR Peptides to Inhibit Undruggable Cancer Target (PQ18)R01CA170820 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROBERTS, RICHARD W, TAKAHASHI, TERRY TORAO · 2012 to 2015
$1.8M
NCI NIH HHS P01 CA132681NCI NIH HHS R01 CA170820NIAID NIH HHS R01 AI068978NIBIB NIH HHS R01 EB017206
6 · The paper itself

Abstract

Although chimeric antigen receptor (CAR)-engineered T cell therapy has achieved encouraging clinical trial results for treating hematological cancers, further optimization can likely expand this therapeutic success to more patients and other cancer types. Most CAR constructs used in clinical trials incorporate single chain variable fragment (scFv) as the extracellular antigen recognition domain. The immunogenicity of nonhuman scFv could cause host rejection against CAR T cells and compromise their persistence and efficacy. The limited availability of scFvs and slow discovery of new monoclonal antibodies also limit the development of novel CAR constructs. Adnectin, a class of affinity molecules derived from the tenth type III domain of human fibronectin, can be an alternative to scFv as an antigen-binding moiety in the design of CAR molecules. We constructed adnectin-based CARs targeting epithelial growth factor receptor (EGFR) and found that compared to scFv-based CAR, T cells engineered with adnectin-based CARs exhibited equivalent cell-killing activity against target H292 lung cancer cells in vitro and had comparable antitumor efficacy in xenograft tumor-bearing mice in vivo. In addition, with optimal affinity tuning, adnectin-based CAR showed higher selectivity on target cells with high EGFR expression than on those with low expression. This new design of adnectin CARs can potentially facilitate the development of T cell immunotherapy for cancer and other diseases.

Indexed as

Amino Acid SequenceAnimalsCell Line, TumorErbB ReceptorsFemaleFibronectinsGene ExpressionHumansImmunotherapy, AdoptiveLung NeoplasmsLymphocyte TransfusionMicePlasmidsProtein DomainsReceptors, Antigen, T-CellRecombinant Fusion ProteinsEGFR protein, humanErbB ReceptorsFibronectinsReceptors, Antigen, T-CellRecombinant Fusion ProteinsSingle-Chain Antibodiesadnectinadoptive T cell therapy (ACT)chimeric antigen receptor (CAR)epithelial growth factor receptor (EGFR)single chain variable fragment (scFv)

Identifiers

PMID28784559
PMCPMC5675441
OpenAlexW2739413729

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.