Evidence map›Paper›PMID 41556618›Full record

ArticleProtein science : a publication of the Protein Society2026

Tetravalent antibodies are more potent and efficacious erythropoiesis-stimulating agents than erythropoietin in vivo.

Jarrett J Adams, Levi L Blazer, Jacky Chung, Minoo Karimi, Taylor Davidson, Bailey Blair, Carlos Waddle, Craig A Hokanson, Heather A Bruce, Alexander U Singer and 11 more

Abstract read
In one paragraph

Article in Protein science : a publication of the Protein Society, 2026. 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. 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

21 authors.

Jarrett J AdamsAnvil Institute for Systems Biologics, Toronto, Ontario, Canada.
Levi L BlazerAnvil Institute for Systems Biologics, Toronto, Ontario, Canada.
Jacky ChungAnvil Institute for Systems Biologics, Toronto, Ontario, Canada.
Minoo KarimiDépartement de Biochimie, Université de Montréal, Montréal, Québec, Canada.
Taylor DavidsonDepartments of Internal Medicine and Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Bailey BlairDepartments of Internal Medicine and Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Carlos WaddleDepartments of Internal Medicine and Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Craig A HokansonSimisco Biosciences, Hayward, California, USA.
Heather A BruceAnvil Institute for Systems Biologics, Toronto, Ontario, Canada.
Alexander U SingerAnvil Institute for Systems Biologics, Toronto, Ontario, Canada.
Eva-Maria TombakIcosagen, Tartu, Estonia.
Kiira GildemannIcosagen, Tartu, Estonia.
Nele TambergIcosagen, Tartu, Estonia.
Kaja KiiverIcosagen, Tartu, Estonia.
Mart UstavIcosagen, Tartu, Estonia.
Yue MaDepartments of Internal Medicine and Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Luigi ColomboEPOK Therapeutics, Toronto, Ontario, Canada.
Lily Jun-Shen HuangDepartments of Internal Medicine and Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Stephen W MichnickDépartement de Biochimie, Université de Montréal, Montréal, Québec, Canada.
Orson W MoeEPOK Therapeutics, Toronto, Ontario, Canada.
Sachdev S SidhuAnvil Institute for Systems Biologics, Toronto, Ontario, Canada.

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI STEVEN E EALICK · 2018 to 2026
$34.2M
JAK2 signaling in erythropoiesisR01HL089966 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI LILY JUNSHEN HUANG · 2007 to 2026
$7.4M
Pathogenesis of Uric Acid Nephrolithiasis: The Multifaceted Role of Renal LipidsR01DK081423 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI MAALOUF, NAIM M, MOE, ORSON W · 2009 to 2023
$6.1M
Origin of Excess Acid in Uric Acid UrolithiasisR01DK115703 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI BROWNING, JEFFREY D, MOE, ORSON W · 2019 to 2023
$2.2M
Lymphatics and lymphangiogenesis in kidney function and inflammationR01DK119497 · NIDDK · TEXAS A&M UNIVERSITY · PI RUTKOWSKI, JOSEPH MICHAEL · 2020 to 2024
$2.1M
The Relation of Soluble Klotho with Cardiovascular Disease, Chronic Kidney Disease Progression, and Blood Pressure in the Systolic Blood Pressure Intervention TrialR01DK128208 · NIDDK · TUFTS MEDICAL CENTER · PI DREW, DAVID ALAN, NEYRA, JAVIER A. · 2021 to 2025
$1.6M
Canada Foundation for Innovation IOF-33363Center of Mineral Metabolism Endowed Professor Collaborative Research Support GrantCharles Pak FoundationCIHR MOP-136944CIHR PJT-159640NHLBI NIH HHS R01 HL089966NIDDK NIH HHS R01 DK081423NIDDK NIH HHS R01 DK115703NIDDK NIH HHS R01 DK119497NIDDK NIH HHS R01 DK128208NIGMS NIH HHS P30 GM124165NIH HHS R01 DK081423NIH HHS R01 DK115703NIH HHS R01 DK119497NIH HHS R01 DK128208NIH HHS R01 HL089966
6 · The paper itself

Abstract

Recent studies have shown that tetravalent antibodies are potent and efficacious agonists of the erythropoietin (EPO) receptor (EPOR) both in vitro and in vivo. To identify antibody-based erythropoiesis-stimulating agents (ESAs) with therapeutic potential, we evaluated various tetravalent antibody formats for EPOR agonism and key biophysical properties necessary for biologic drug development. We identified two distinct tetravalent antibody formats that strongly stimulated the growth of UT7/Epo cells, which rely on EPOR signaling for proliferation. Moreover, one of these formats exhibited ideal biophysical characteristics for drug development. This format consisted of a diabody (Db) and two antigen-binding fragment (Fab) arms fused to the N- and C-termini of an Fc domain, respectively, to form a tetravalent Db-Fc-Fab (EPRA-0322). In a mouse model expressing the human EPOR, EPRA-0322 induced erythropoiesis with greater potency, efficacy, and duration than darbepoetin, a hyperglycosylated EPO currently used in clinical practice. These findings highlight tetravalent antibodies, and the Db-Fc-Fab format in particular, as promising next-generation ESAs suitable for large-scale production and clinical use.

Indexed as

ErythropoiesisErythropoietinHematinicsReceptors, ErythropoietinAnimalsHumansMiceErythropoietinHematinicsReceptors, Erythropoietinagonistantibodyantibody polymerdiabodydimerdrug designEPOEPORerythropoiesishelical ultrastructureprotein engineering

Identifiers

PMID41556618
PMCPMC12817467

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.