Evidence map›Paper›PMID 40925997›Full record

ArticleNature biotechnology2026

Antibody-bottlebrush prodrug conjugates for targeted cancer therapy.

Bin Liu, Hung V-T Nguyen, Yivan Jiang, Aiden X Wang, Valerie Lensch, Zehao Sun, Zane H Boyer, Philip A Raftopoulos, Yutong Dai, Piper L MacNicol and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

22 authors.

Bin LiuDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1736-9392
Hung V-T NguyenDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6945-4057
Yivan JiangWindow Therapeutics, Boston, MA, USA.
Aiden X WangDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6335-9836
Valerie LenschDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0371-2866
Zehao SunDepartment of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, USA.ORCID http://orcid.org/0000-0002-9720-694X
Zane H BoyerMerck Center for Catalysis at Princeton University, Princeton, NJ, USA.
Philip A RaftopoulosMerck Center for Catalysis at Princeton University, Princeton, NJ, USA.
Yutong DaiDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0009-0009-1188-4124
Piper L MacNicolDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Yuyan WangDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nidhi JyotsanaGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Wencong WangDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Sachin BhagchandaniDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Sanjana HemdevWindow Therapeutics, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6505-1023
Peyton ShiehDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Samantha L KristufekDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Magalie BoucherDivision of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0009-0008-6293-6775
Michael DownesGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Ronald M EvansGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-9986-5965
David W C MacMillanMerck Center for Catalysis at Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0001-6447-0587
Jeremiah A JohnsonDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA. jaj2109@mit.edu.ORCID http://orcid.org/0000-0001-9157-6491

Funding

Photoredox Catalysis Applications in Organometallics and Chemical BiologyR35GM134897 · NIGMS · PRINCETON UNIVERSITY · PI David W MacMillan · 2020 to 2026
$6.3M
Organic nanoparticles for dual MRI-guided therapeutic selection and ovarian cancer drug deliveryR01CA220468 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jeremiah Allen Johnson · 2017 to 2026
$4.9M
NCI NIH HHS R01 CA220468NIGMS NIH HHS R35 GM134897U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 2R01CA220468-06A1
6 · The paper itself

Abstract

Antibody-drug conjugates (ADCs) are effective targeted therapeutics but are limited in their ability to incorporate less-potent payloads, varied drug mechanisms of action, different drug release mechanisms and tunable drug-to-antibody ratios. Here we introduce a technology to overcome these limitations called 'antibody-bottlebrush prodrug conjugates' (ABCs). An ABC consists of an IgG1 monoclonal antibody covalently conjugated to the terminus of a compact bivalent bottlebrush prodrug that has payloads bound through cleavable linkers and polyethylene glycol branches. This design enables the synthesis of ABCs with tunable average drug-to-antibody ratios up to two orders of magnitude greater than those of traditional ADCs. We demonstrate the functional flexibility and manufacturing efficiency of this technology by synthesizing more than 10 different ABCs targeting either HER2 or MUC1 using drugs with potencies spanning several orders of magnitude as well as imaging agents for ABC visualization and photocatalysts for proximity-based labeling of the ABC interactome. ABCs display high target engagement, high cell uptake and improved efficacy in tumor models compared to conventional HER2-targeted ADCs, suggesting promise for clinical translation.

Indexed as

ImmunoconjugatesNeoplasmsProdrugsAnimalsAntibodies, MonoclonalAntineoplastic AgentsCell Line, TumorErb-b2 Receptor Tyrosine KinasesHumansImmunoglobulin GMiceMucin-1Antibodies, MonoclonalAntineoplastic AgentsERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesImmunoconjugatesImmunoglobulin GMUC1 protein, humanMucin-1Prodrugs

Identifiers

PMID40925997
PMCPMC12425459

What Socratic holds

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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 Socratic graph.