Evidence map›Paper›PMID 40532576›Full record

ArticleBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2025

Targeting prostate cancer with site-specific antibody-drug conjugates enabled by tandemly fused ADP-ribosyl cyclases.

Lei Zhang, Mashael F Aldossari, Arshad J Ansari, Guoyun Kao, Sunny H Kim, Thuc Oanh Hoang, Kaiyu Shen, Zeyu Zhang, Srinivasarao Singireddi, Zekun Li and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2025. 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. Article
  2. Review
  3. Synthesis of Bispecific Conjugates by ADP-Ribosyl Cyclases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    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.

Lei ZhangDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Mashael F AldossariDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA; Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Arshad J AnsariDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Guoyun KaoDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Sunny H KimDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Thuc Oanh HoangDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Kaiyu ShenDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Zeyu ZhangDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Srinivasarao SingireddiDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Zekun LiDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Yuanteng ZhaoDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Po-Wen YuDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Fariborz NasertorabiDepartments of Biological Sciences and Chemistry, Bridge Institute, Michelson Center for Convergent Bioscience, USC Structure Biology Center, University of Southern California, Los Angeles, CA 90089, USA.
Benjamin B KatzDepartment of Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Ling LiDepartment of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Yong ZhangDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA; Department of Chemistry, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA; Research Center for Liver Diseases, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: yongz@usc.edu.

Funding

Chemistry and Biology of ADP-Ribosylation-Dependent SignalingR35GM137901 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Yong Zhang · 2020 to 2026
$2.5M
Reprogramming Exosomes for Biomedical ApplicationsR01EB031830 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZHANG, YONG · 2021 to 2024
$2.1M
Reprogramming Exosomes for Novel Immunotherapy of Triple Negative Breast CancerR01CA276240 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Yong Zhang · 2023 to 2026
$2.0M
NCI NIH HHS R01 CA276240NIBIB NIH HHS R01 EB031830NIGMS NIH HHS R35 GM137901
6 · The paper itself

Abstract

Antibody-drug conjugates (ADCs) bring superior efficacy and safety profiles to the clinic by harnessing the power of biologics and chemotherapy. Despite numerous ADCs at different preclinical and clinical stages, homogeneous ADC with increased numbers of payloads conjugated at specific positions are still desired for enhanced pharmacological properties. To generate site-specifically conjugated ADCs with greater drug-to-antibody ratios (DARs), monoclonal antibodies targeting prostate-specific membrane antigens (PSMA) were genetically fused with tandem CD38 enzymes, a member of the ADP-ribosyl cyclase family. The resulting antibody-CD38 fusions coupled with its dinucleotide substrate-derived drug linker facilitate generation of ADP-ribosyl cyclase-enable ADCs (ARC-ADCs) carrying 2, 4, 6, and 8 tubulin inhibitors. In vitro and in vivo studies indicated highly potent and selective cytotoxicity against human PSMA-expressing prostate cancer cells for the anti-PSMA ARC-ADC with a DAR of 6. This proof-of-concept study demonstrates feasibility of producing site-specific ARC-ADCs with increased DARs by tandemly fused CD38 and generates candidate ADCs for targeting prostate tumors.

Indexed as

ADP-ribosyl CyclaseADP-ribosyl Cyclase 1Antibodies, MonoclonalImmunoconjugatesProstatic NeoplasmsAnimalsAntigens, SurfaceCell Line, TumorGlutamate Carboxypeptidase IIHumansMaleMiceMice, NudeTubulin ModulatorsXenograft Model Antitumor AssaysADP-ribosyl CyclaseADP-ribosyl Cyclase 1Antibodies, MonoclonalAntigens, SurfaceFOLH1 protein, humanGlutamate Carboxypeptidase IIImmunoconjugatesTubulin ModulatorsADP-ribosyl cyclaseAntibody-drug conjugateDrug deliveryProstate cancerTargeted therapy

Identifiers

PMID40532576
PMCPMC12286717

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Registered trials

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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.