Evidence map›Paper›PMID 24944121›Full record

ArticleMolecular cancer therapeutics2014

Preclinical evaluation of multistep targeting of diasialoganglioside GD2 using an IgG-scFv bispecific antibody with high affinity for GD2 and DOTA metal complex.

Sarah M Cheal, Hong Xu, Hong-fen Guo, Pat B Zanzonico, Steven M Larson, Nai-Kong Cheung

Abstract read
In one paragraph

Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
–field-weighted citation impact
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

40 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a BivalentJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024
    Article
  5. Review
  6. Efficacy of HER2-Targeted IntraperitonealJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023
    Article
  7. Clearing and Masking Agents in Pretargeting Strategies.Pharmaceuticals (Basel, Switzerland) · 2023
    Review
  8. Article
  9. Article
  10. Review
  11. Pretargeting: A Path Forward for Radioimmunotherapy.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022
    Review
  12. Article
  13. Article
  14. A Self-Assembling and Disassembling (SADA) Bispecific Antibody (BsAb) Platform for Curative Two-step Pretargeted Radioimmunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
  15. Targets and Antibody Formats for Immunotherapy of Neuroblastoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020
    Review
  16. Review
  17. AnBioconjugate chemistry · 2020
    Article
  18. Article
  19. Review
  20. 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

6 authors.

Sarah M ChealAuthors' Affiliations: Departments of Radiology and.
Hong XuPediatrics;
Hong-fen GuoPediatrics;
Pat B ZanzonicoMolecular Pharmacology and Therapy Service; and.
Steven M LarsonMolecular Pharmacology and Therapy Service; and Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York.
Nai-Kong CheungPediatrics; Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York cheungn@mskcc.org.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
SPORE In Prostate CancerP50CA092629 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Yu Chen, MICHAEL J MORRIS · 2001 to 2026
$63.0M
Tumor Evolution and Changes in MetabolismP50CA086438 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI RIVIERI, ISABELLE · 2000 to 2015
$29.9M
Molecular Imaging: Training for OncologyR25CA096945 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI HRICAK, HEDVIG · 2002 to 2013
$5.2M
Memorial Sloan Kettering Small Animal Imaging ResearchR24CA083084 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI KOUTCHER, JASON ARTHUR · 1999 to 2006
$4.4M
NanoSPECT/CT for Oncology ResearchS10RR028889 · NCRR · SLOAN-KETTERING INST CAN RESEARCH · PI ZANZONICO, PAT B · 2011 to 2011
$907k
SHARED INSTRUMENT: FOCUS MICROPET: CANCERS10RR020892 · NCRR · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI LARSON, STEVEN MARK · 2005 to 2005
$499k
NCI NIH HHS P30 CA008748NCI NIH HHS P30-CA08748NCI NIH HHS P50 CA086438NCI NIH HHS P50 CA092629NCI NIH HHS P50-CA86438NCI NIH HHS P50-CA92629NCI NIH HHS R24 CA083084NCI NIH HHS R24-CA83084NCI NIH HHS R25 CA096945NCI NIH HHS R25-CA096945NCRR NIH HHS 1 S10RR020892-01NCRR NIH HHS 1 S10 RR028889-01NCRR NIH HHS S10 RR020892NCRR NIH HHS S10 RR028889
6 · The paper itself

Abstract

Bispecific antibodies (BsAb) have proven to be useful targeting vectors for pretargeted radioimmunotherapy (PRIT). We sought to overcome key PRIT limitations such as high renal radiation exposure and immunogenicity (e.g., of streptavidin-antibody fusions), to advance clinical translation of this PRIT strategy for diasialoganglioside GD2-positive [GD2(+)] tumors. For this purpose, an IgG-scFv BsAb was engineered using the sequences for the anti-GD2 humanized monoclonal antibody hu3F8 and C825, a murine scFv antibody with high affinity for the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complexed with β-particle-emitting radiometals such as (177)Lu and (90)Y. A three-step regimen, including hu3F8-C825, a dextran-based clearing agent, and p-aminobenzyl-DOTA radiolabeled with (177)Lu (as (177)Lu-DOTA-Bn; t1/2 = 6.71 days), was optimized in immunocompromised mice carrying subcutaneous human GD2(+) neuroblastoma (NB) xenografts. Absorbed doses for tumor and normal tissues were approximately 85 cGy/MBq and ≤3.7 cGy/MBq, respectively, with therapeutic indices (TI) of 142 for blood and 23 for kidney. A therapy study (n = 5/group; tumor volume, 240 ± 160 mm(3)) with three successive PRIT cycles (total (177)Lu: ∼33 MBq; tumor dose ∼3,400 cGy), revealed complete tumor response in 5 of 5 animals, with no recurrence up to 28 days after treatment. Tumor ablation was confirmed histologically in 4 of 5 mice, and normal organs showed minimal overall toxicities. All nontreated mice required sacrifice within 12 days (>1.0-cm(3) tumor volume). We conclude that this novel anti-GD2 PRIT approach has sufficient TI to successfully ablate subcutaneous GD2(+)-NB in mice while sparing kidney and bone marrow.

Indexed as

AnimalsAntibodies, BispecificDrug Evaluation, PreclinicalFemaleGangliosidesHumansImmunoglobulin FragmentsImmunoglobulin GLutetiumMiceMice, NudeOctreotideOrganometallic CompoundsRadioimmunotherapyRadiopharmaceuticalsRandom AllocationAntibodies, Bispecificganglioside, GD2GangliosidesImmunoglobulin FragmentsImmunoglobulin GLutetiumOctreotideOrganometallic CompoundsRadiopharmaceuticalsYttrium Radioisotopes

Identifiers

PMID24944121
PMCPMC4221074

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.