Evidence map›Paper›PMID 36190986›Full record

ArticleMolecular cancer therapeutics2023

Antibody-Drug Conjugate Sacituzumab Govitecan Drives Efficient Tissue Penetration and Rapid Intracellular Drug Release.

Anna Kopp, Scott Hofsess, Thomas M Cardillo, Serengulam V Govindan, Jennifer Donnell, Greg M Thurber

Open access · greenAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 2 pooled it
7.3field-weighted citation impact, top 2% 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

61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.

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  6. A modular framework for antibody-drug conjugate biomarkers.Nature reviews. Clinical oncology · 2026
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1 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 2 institutions in 1 country.

Anna KoppDepartment of Chemical Engineering, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-2799-4581
Scott HofsessGilead Sciences, Inc., Morris Plains, New Jersey.ORCID 0000-0002-8465-4065
Thomas M CardilloGilead Sciences, Inc., Morris Plains, New Jersey.ORCID 0000-0002-9427-8358
Serengulam V GovindanGilead Sciences, Inc., Morris Plains, New Jersey.ORCID 0000-0003-4920-922X
Jennifer DonnellGilead Sciences, Inc., Morris Plains, New Jersey.ORCID 0000-0002-0595-7835
Greg M ThurberDepartment of Chemical Engineering, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-7570-2080
Immunomedics (United States) · USUniversity of Michigan · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
Maximizing Antibody Drug Conjugate Efficacy through Multiple Mechanisms of ActionR35GM128819 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Greg Thurber · 2018 to 2026
$2.8M
NCI NIH HHS P30 CA046592NIGMS NIH HHS R35 GM128819
6 · The paper itself

Abstract

Antibody-drug conjugates (ADC) are a rapidly growing class of targeted cancer treatments, but the field has experienced significant challenges from their complex design. This study examined the multiscale distribution of sacituzumab govitecan (SG; Trodelvy), a recently clinically approved ADC, to clarify the mechanism(s) of efficacy given its unique design strategy. We employed a multiscale quantitative pharmacokinetic approach, including near-infrared fluorescence imaging, single-cell flow cytometry measurements, payload distribution via γH2AX pharmacodynamic staining, and a novel dual-labeled fluorescent technique to track the ADC and payload in a high trophoblast cell-surface antigen 2 expression xenograft model of gastric cancer (NCI-N87). We found that rapid release of the SN-38 payload from the hydrolysable linker inside cells imparts more DNA damage in vitro and in vivo than an ADC with a more stable enzyme cleavable linker. With SG, little to no extracellular payload release in the tumor was observed using a dual-labeled fluorescence technique, although bystander effects were detected. The high dosing regimen allowed the clinical dose to reach the majority of cancer cells, which has been linked to improved efficacy. In addition, the impact of multiple doses (day 1 and day 8) of a 21-day cycle was found to further improve tissue penetration despite not changing tumor uptake [percent injected dose per gram (%ID/g)] of the ADC. These results show increased ADC efficacy with SG can be attributed to efficient tumor penetration and intracellular linker cleavage after ADC internalization. This quantitative approach to study multiscale delivery can be used to inform the design of next-generation ADCs and prodrugs for other targets.

Indexed as

ImmunoconjugatesStomach NeoplasmsAntibodies, Monoclonal, HumanizedCamptothecinCell Line, TumorDrug LiberationHumansAntibodies, Monoclonal, HumanizedCamptothecinImmunoconjugatessacituzumab govitecan

Identifiers

PMID36190986
PMCPMC9812893
OpenAlexW4300689840

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.