Evidence map›Paper›PMID 33856579›Full record

ArticleThe AAPS journal2021

Quantitative Evaluation of the Effect of Antigen Expression Level on Antibody-Drug Conjugate Exposure in Solid Tumor.

David Bussing, Sharad Sharma, Zhe Li, Lyndsey F Meyer, Dhaval K Shah

Abstract read
PubMed Publisher
In one paragraph

Article in The AAPS journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 12% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Could a Long-Acting Prodrug of SN-38 be Efficacious in Sacituzumab Govitecan-Resistant Tumors?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Article
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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

5 authors at 1 institution in 1 country.

David BussingDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, New York, USA.
Sharad SharmaDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, New York, USA. sharadsharma09@hotmail.com.
Zhe LiDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, New York, USA.
Lyndsey F MeyerDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, New York, USA.
Dhaval K ShahDepartment of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, New York, USA. dshah4@buffalo.edu.
University at Buffalo, State University of New York · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody-drug conjugates (ADCs) rely on high expression of target antigens on cancer cells to effectively enter the cell and release a cytotoxic payload. Previous studies have shown that ADC efficacy is not always tied to antigen expression. However, our recent in vitro study suggests a linear relationship between antigen expression and the intracellular levels of the ADC payload. In this study, we have explored the relationship between antigen expression and intratumoral ADC exposure in vivo. Using trastuzumab-vc-MMAE (T-vc-MMAE) and four cell lines with varying expression of human epithelial growth factor receptor 2 (HER2), the pharmacokinetics of total trastuzumab, released ("free") MMAE, and total MMAE were evaluated in a tumor xenograft model. Nude mice were implanted with tumors originating from BT-474, MDA-MB-453, MCF-7, and MDA-MB-468 cell lines and dosed with 10 mg/kg or 1 mg/kg of ADC. Observed data were mathematically characterized using a mechanism-based PK model. A strong positive correlation was observed between antigen expression levels and free/total MMAE exposure (R

Indexed as

AnimalsAntigens, NeoplasmAntineoplastic Agents, ImmunologicalBystander EffectCell Line, TumorErb-b2 Receptor Tyrosine KinasesHumansImmunoconjugatesMiceModels, BiologicalNeoplasmsOligopeptidesTissue DistributionTrastuzumabXenograft Model Antitumor AssaysAntigens, NeoplasmAntineoplastic Agents, ImmunologicalERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesImmunoconjugatesOligopeptidesTrastuzumabtrastuzumab-vc-MMAEantibody–drug conjugatesantigen expression levelsolid tumorsystems PK modeltumor pharmacokinetics

Identifiers

PMID33856579
OpenAlexW3155111968

What OpenQuestion holds

Textmetadata
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.