Evidence map›Paper›PMID 27933313›Full record

ArticleMolecular therapy oncolytics2016

Genetic engineering of chimeric antigen receptors using lamprey derived variable lymphocyte receptors.

Robert Moot, Sunil S Raikar, Lauren Fleischer, Melissa Querrey, Daniel E Tylawsky, Hirotomo Nakahara, Christopher B Doering, H Trent Spencer

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy oncolytics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 8% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Pooled it
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  13. The variable lymphocyte receptor as an antibody alternative.Current opinion in biotechnology · 2018
    Review
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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

8 authors at 3 institutions in 1 country.

Robert MootDepartment of Molecular and Systems Pharmacology, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine , Atlanta, Georgia, USA.
Sunil S RaikarDepartment of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine , Atlanta, Georgia, USA.
Lauren FleischerDepartment of Molecular and Systems Pharmacology, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine , Atlanta, Georgia, USA.
Melissa QuerreyDepartment of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine , Atlanta, Georgia, USA.
Daniel E TylawskyDepartment of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine , Atlanta, Georgia, USA.
Hirotomo NakaharaDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine , Atlanta, Georgia, USA.
Christopher B DoeringDepartment of Molecular and Systems Pharmacology, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, Georgia, USA; Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, Georgia, USA.
H Trent SpencerDepartment of Molecular and Systems Pharmacology, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, Georgia, USA; Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, Georgia, USA.
Emory University · USAflac (United States) · USCenter for Cancer and Blood Disorders · US

Funding

Graduate Training in the Pharmacological StudiesT32GM008602 · NIGMS · EMORY UNIVERSITY · PI HALL, RANDY A. · 1996 to 2021
$5.1M
VLR-CART Cancer ImmunotherapyR43CA192710 · NCI · NOVAB, INC. · PI CANNON, LOVICK EDWARD, COOPER, MAX DALE · 2014 to 2014
$149k
NCI NIH HHS R43 CA192710NIGMS NIH HHS T32 GM008602
6 · The paper itself

Abstract

Chimeric antigen receptors (CARs) are used to redirect effector cell specificity to selected cell surface antigens. Using CARs, antitumor activity can be initiated in patients with no prior tumor specific immunity. Although CARs have shown promising clinical results, the technology remains limited by the availability of specific cognate cell target antigens. To increase the repertoire of targetable tumor cell antigens we utilized the immune system of the sea lamprey to generate directed variable lymphocyte receptors (VLRs). VLRs serve as membrane bound and soluble immune effectors analogous but not homologous to immunoglobulins. They have a fundamentally different structure than immunoglobulin (Ig)-based antibodies while still demonstrating high degrees of specificity and affinity. To test the functionality of VLRs as the antigen recognition domain of CARs, two VLR-CARs were created. One contained a VLR specific for a murine B cell leukemia and the other contained a VLR specific for the human T cell surface antigen, CD5. The CAR design consisted of the VLR sequence, myc-epitope tag, CD28 transmembrane domain, and intracellular CD3ζ signaling domain. We demonstrate proof of concept, including gene transfer, biosynthesis, cell surface localization, and effector cell activation for multiple VLR-CAR designs. Therefore, VLRs provide an alternative means of CAR-based cancer recognition.

Identifiers

PMID27933313
PMCPMC5142425
OpenAlexW2560818544

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.