Evidence map›Paper›PMID 25542634›Full record

ArticleCancer immunology research2015

Retargeting T cells to GD2 pentasaccharide on human tumors using Bispecific humanized antibody.

Hong Xu, Ming Cheng, Hongfen Guo, Yuedan Chen, Morgan Huse, Nai-Kong V Cheung

Open access · bronzeAbstract read
In one paragraph

Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

65 citing papers in PubMed, 94 citations in OpenAlex.

  1. Review
  2. Review
  3. Immunotherapeutic Strategies Targeting GD2-Expressing Malignancies.Advances in experimental medicine and biology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. F77 antigen is a promising target for adoptive T cell therapy of prostate cancer.Biochemical and biophysical research communications · 2023
    Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

5 more citing papers are in PubMed but not listed here.

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.

Hong XuDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
Ming ChengDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
Hongfen GuoDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
Yuedan ChenDepartment of Immunology, Memorial Sloan Kettering Cancer Center, New York, New York.
Morgan HuseDepartment of Immunology, Memorial Sloan Kettering Cancer Center, New York, New York.
Nai-Kong V CheungDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York. cheungn@mskcc.org.
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 P30 CA008748
6 · The paper itself

Abstract

Anti-disialoganglioside GD2 IgG antibodies have shown clinical efficacy in solid tumors that lack human leukocyte antigens (e.g., neuroblastoma) by relying on Fc-dependent cytotoxicity. However, there are pain side effects secondary to complement activation. T-cell retargeting bispecific antibodies (BsAb) also have clinical potential, but it is thus far only effective against liquid tumors. In this study, a fully humanized hu3F8-BsAb was developed, in which the anti-CD3 huOKT3 single-chain Fv fragment (ScFv) was linked to the carboxyl end of the anti-GD2 hu3F8 IgG1 light chain, and was aglycosylated at N297 of Fc to prevent complement activation and cytokine storm. In vitro, hu3F8-BsAb activated T cells through classic immunologic synapses, inducing GD2-specific tumor cytotoxicity at femtomolar EC50 with >10⁵-fold selectivity over normal tissues, releasing Th1 cytokines (TNFα, IFNγ, and IL2) when GD2⁺ tumors were present. In separate murine neuroblastoma and melanoma xenograft models, intravenous hu3F8-BsAb activated T cells in situ and recruited intravenous T cells for tumor ablation, significantly prolonging survival from local recurrence or from metastatic disease. Hu3F8-BsAb, but not control BsAb, drove T cells and monocytes to infiltrate tumor stroma. These monocytes were necessary for sustained T-cell proliferation and/or survival and contributed significantly to the antitumor effect. The in vitro and in vivo antitumor properties of hu3F8-BsAb and its safety profile support its further clinical development as a cancer therapeutic, and provide the rationale for exploring aglycosylated IgG-scFv as a structural platform for retargeting human T cells.

Indexed as

AnimalsAntibodies, BispecificCD3 ComplexCell Line, TumorCell ProliferationGangliosidesHumansImmunoglobulin GMelanomaMiceMice, Inbred BALB CMice, KnockoutMonocytesNeuroblastomaSingle-Chain AntibodiesT-LymphocytesAntibodies, BispecificCD3 Complexganglioside, GD2GangliosidesImmunoglobulin GSingle-Chain Antibodies

Identifiers

PMID25542634
PMCPMC4351131
OpenAlexW2100033620

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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.