Evidence map›Paper›PMID 24895182›Full record

ArticleInternational journal of cancer2015

Structural design of disialoganglioside GD2 and CD3-bispecific antibodies to redirect T cells for tumor therapy.

Ming Cheng, Mahiuddin Ahmed, Hong Xu, Nai-Kong V Cheung

Open access · bronzeAbstract read
In one paragraph

Article in International journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

38 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
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  4. Immunotherapeutic Strategies Targeting GD2-Expressing Malignancies.Advances in experimental medicine and biology · 2026
    Review
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  20. The Role of Sphingolipids in Cancer Immunotherapy.International journal of molecular sciences · 2021
    Review
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

4 authors at 1 institution in 1 country.

Ming ChengDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
Mahiuddin Ahmed
Hong Xu
Nai-Kong V Cheung
Memorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS 2 P30CA008748-48NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Antibody-based immunotherapy has proven efficacy for patients with high-risk neuroblastoma. However, despite being the most efficient tumoricidal effectors, T cells are underutilized because they lack Fc receptors. Using a monovalent single-chain fragment (ScFv) platform, we engineered tandem scFv bispecific antibodies (BsAbs) that specifically target disialoganglioside (GD2) on tumor cells and CD3 on T cells. Structural variants of BsAbs were constructed and ranked based on binding to GD2, and on competency in inducing T-cell-mediated tumor cytotoxicity. In vitro thermal stability and binding measurements were used to characterize each of the constructs, and in silico molecular modeling was used to show how the orientation of the variable region heavy (VH) and light (VL) chains of the anti-GD2 ScFv could alter the conformations of key residues responsible for high affinity binding. We showed that the VH-VL orientation, the (GGGGS)3 linker, disulfide bond stabilization of scFv, when combined with an affinity matured mutation provided the most efficient BsAb to direct T cells to lyse GD2-positive tumor cells. In vivo, the optimized BsAb could efficiently inhibit melanoma and neuroblastoma xenograft growth. These findings provide preclinical validation of a structure-based method to assist in designing BsAb for T-cell-mediated therapy.

Indexed as

AnimalsAntibodies, BispecificAntibodies, MonoclonalBlotting, WesternCD3 ComplexCell ProliferationEnzyme-Linked Immunosorbent AssayFlow CytometryGangliosidesHumansImmunotherapyLymphocyte ActivationMelanomaMiceMice, Inbred BALB CMice, NudeAntibodies, BispecificAntibodies, MonoclonalCD3 Complexganglioside, GD2GangliosidesSingle-Chain Antibodiesbispecificitydisialogangliosideimmunotherapyneuroblastomastructure

Identifiers

PMID24895182
PMCPMC4517675
OpenAlexW1954768511

What OpenQuestion holds

Textmetadata
LicenceTDM
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.