Evidence map›Paper›PMID 40626955›Full record

ArticleChembiochem : a European journal of chemical biology2025

Design and Characterization of Prodrugged Anti-CTLA-4 Antibodies.

Sayumi Yamazoe, Mary Huber, Srikanth Kotapati, Rahima Akter, Aarti Jashnani, Suprit Deol, Christine Bee, John Engelhart, Yam B Poudel, Stanley Krystek and 6 more

Abstract read
In one paragraph

Article in Chembiochem : a European journal of chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Design and Characterization of Prodrugged Anti-CTLA-4 Antibodies.Chembiochem : a European journal of chemical biology · 2025
    Article
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

16 authors.

Sayumi YamazoeResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.ORCID https://orcid.org/0000-0002-2169-7674
Mary HuberResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
Srikanth KotapatiResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
Rahima AkterResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
Aarti JashnaniResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
Suprit DeolResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
Christine BeeResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
John EngelhartResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
Yam B PoudelResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
Stanley KrystekResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
John HaugnerResearch and Development, Bristol Myers Squibb, Cambridge, MA, 02141, USA.
Mohan SrinivasanResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
Arvind RajpalResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
Yong ZhangResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
Pavel StropResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.
Chetana RaoResearch and Development, Bristol Myers Squibb, Redwood City, CA, 94063, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Therapeutic antibodies are widely used to treat diseases like cancer and inflammatory conditions by binding with high specificity to their molecular targets. Masking is a strategy to mitigate undesirable activity in nontarget tissues, improving safety and pharmacokinetic (PK) profiles by reducing target-mediated drug disposition. In this article, masking of an anti-CTLA-4 antibody by conjugating a large PEG molecule to specific sites on the antibody is explored. While anti-CTLA-4 immunotherapy benefits solid tumor treatment, its adverse events limit its utility. Multiple conjugation sites within the complementarity-determining regions and adjacent framework regions are evaluated to attenuate CTLA-4 binding. The optimal site for maximizing masking efficiency is identified, allowing for efficient bioconjugation and functional restoration upon exposure to a cleaving enzyme in the tumor microenvironment. The prodrugged antibody exhibits reduced binding to CTLA-4 and Fc gamma receptors, high stability, and an extended half-life in a mouse model. This technology has the potential to improve the PK profile and safety attributes of therapeutic antibodies.

Indexed as

Antibodies, MonoclonalCTLA-4 AntigenDrug DesignProdrugsAnimalsHumansMiceAntibodies, MonoclonalCTLA-4 AntigenProdrugsantibody‐drug‐conjugateimmune checkpoint inhibitorspharmacokineticsprodruggingsite‐specific conjugation

Identifiers

PMID40626955
PMCPMC12631005

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.