Evidence map›Paper›PMID 26673402›Full record

ArticleJournal for immunotherapy of cancer2015

Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors.

Joanne A Hammill, Heather VanSeggelen, Christopher W Helsen, Galina F Denisova, Carole Evelegh, Daniela G M Tantalo, Jennifer D Bassett, Jonathan L Bramson

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
1.7field-weighted citation impact, top 13% 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

47 citing papers in PubMed, 78 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

8 authors at 1 institution in 1 country.

Joanne A HammillDepartment Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON Canada.
Heather VanSeggelenDepartment Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON Canada.
Christopher W HelsenDepartment Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON Canada.
Galina F DenisovaDepartment Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON Canada.
Carole EveleghDepartment Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON Canada.
Daniela G M TantaloDepartment Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON Canada.
Jennifer D BassettDepartment Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON Canada.
Jonathan L BramsonDepartment Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON Canada.
McMaster University Medical Centre · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAdoptive cell transfer of tumor-specific T lymphocytes (T cells) is proving to be an effective strategy for treating established tumors in cancer patients. One method of generating these cells is accomplished through engineering bulk T cell populations to express chimeric antigen receptors (CARs), which are specific for tumor antigens. Traditionally, these CARs are targeted against tumor antigens using single-chain antibodies (scFv). Here we describe the use of a designed ankyrin repeat protein (DARPin) as the tumor-antigen targeting domain.

methodsWe prepared second generation anti-HER2 CARs that were targeted to the tumor antigen by either a DARPin or scFv. The CARs were engineered into human and murine T cells. We then compared the ability of CARs to trigger cytokine production, degranulation and cytotoxicity.

resultsThe DARPin CARs displayed reduced surface expression relative to scFv CARs in murine cells but both CARs were expressed equally well on human T cells, suggesting that there may be a processing issue with the murine variants. In both the murine and human systems, the DARPin CARs were found to be highly functional, triggering cytokine and cytotoxic responses that were similar to those triggered by the scFv CARs.

conclusionsThese findings demonstrate the utility of DARPins as CAR-targeting agents and open up an avenue for the generation of CARs with novel antigen binding attributes.

Indexed as

CancerCARChimeric antigen receptorDARPinDesigned ankyrin repeat proteinImmunotherapy

Identifiers

PMID26673402
PMCPMC4678647
OpenAlexW2221239533

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.