Evidence map›Paper›PMID 41896977›Full record

ArticleJournal of experimental & clinical cancer research : CR2026

RGX-019-MMAE inhibits leukemia progression by targeting MER proto-oncogene tyrosine kinase (MERTK) in acute myeloid leukemia.

Anudishi Tyagi, Maryam Siddiqui, Amanda Eckstrom, Isabel Kurth, Shugaku Takeda, Priyanka Sharma, Gautam Borthakur, Bin Yuan, Hussein A Abbas, Vivek Anand and 4 more

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In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Anudishi Tyagi *Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Maryam Siddiqui *Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Amanda EckstromDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Isabel KurthInspirna, Inc., New York, New York, USA.
Shugaku Takeda *Inspirna, Inc., New York, New York, USA.
Priyanka SharmaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Gautam BorthakurDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Bin YuanDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Hussein A AbbasDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Vivek AnandDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jenny BorgmanDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Steven KornblauDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Abhishek MaitiDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
V Lokesh BattulaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. battulav3@vcu.edu.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Kathrin Milbury · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

backgroundMyeloid epithelial reproductive tyrosine kinase (MERTK) receptor is overexpressed in cancers and is associated with poor prognosis. RGX-019-MMAE, a novel humanized IgG1-MMAE antibody-drug conjugate (ADC) (Inspirna, Inc), selectively binds to MERTK with high affinity, resulting in internalization and degradation of the receptor. It then induces cytotoxicity through the release of the payload, MMAE (monomethyl auristatin E), which disrupts mitosis.

methodsMERTK protein expression was analyzed in 818 AML patients using Reverse Phase Protein Arrays (RPPA). Expression was also assessed by flow cytometry in eight AML cell lines and peripheral blood or bone marrow mononuclear cells from five AML patients. Cell lines with the highest MERTK expression were treated with varying doses of RGX-019-MMAE or naked antibody for 120 h, and viability was measured using CellTiter-Glo 2.0. Similarly, primary cells from five AML patients were treated to assess the anti-leukemic effect of RGX-019-MMAE. Further, the combinatorial effects of RGX-019-MMAE with venetoclax (BCL2 inhibitor) were evaluated in vitro.

resultsReverse-phase protein array in 818 primary AML samples revealed significantly high MERTK protein expression in monocytic acute myeloid leukemia (AML), especially in those with PTPN11, RAS, CEBPA mutations, t (9;11) translocation, and high WBC count, suggesting its potential as a therapeutic target in AML. We also observed varying degrees of MERTK expression in AML cell lines, with highest expression in Kasumi-1 and OCI-AML3. Treatment of these cell lines with the anti-MERTK antibody-drug conjugate RGX-019-MMAE resulted in significantly more leukemic cell killing than the control antibody in a dose-dependent manner. We validated this finding in MERTK-expressing primary AML samples expressing MERTK. Interestingly, RGX-019-MMAE had no effect on normal hematopoietic stem cells’ clonogenic potential. Further, treatment with RGX-019-MMAE inhibited AML progression in vivo and significantly prolonged survival of AML xenograft-bearing mice in a dose-dependent manner. Moreover, treatment with RGX-019-MMAE sensitized AML cells to venetoclax in a dose-dependent manner.

conclusionMERTK is overexpressed in AML and could serve as a therapeutic target. Furthermore, RGX-019 MMAE can be used as a novel therapeutic approach for treating AML, especially in treating monocytic subsets of AML.

Indexed as

c-Mer Tyrosine KinaseImmunoconjugatesLeukemia, Myeloid, AcuteOligopeptidesAdultAgedAnimalsCell Line, TumorDisease ProgressionFemaleHumansMaleMiceMiddle AgedProto-Oncogene MasXenograft Model Antitumor Assaysc-Mer Tyrosine KinaseImmunoconjugatesMAS1 protein, humanMERTK protein, humanmonomethyl auristatin EOligopeptidesProto-Oncogene MasAcute myeloid leukemia (AML)Antibody drug conjugate (ADC)Monomethyl auristatin e (MMAE)Myeloid epithelial tyrosine kinase (MERTK)Reverse phase protein arrays (RPPA)

Identifiers

PMID41896977
PMCPMC13032267

What Socratic holds

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LicenceCC BY
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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 Socratic graph.