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Related Concept Videos

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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MicroRNA-142 improves IL1RAP CAR-T cell activity in acute myeloid leukemia.

Kaito Harada1,2, Dandan Zhao1, Miso Park3

  • 1Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA.

Journal of Hematology & Oncology
|November 12, 2025
PubMed
Summary
This summary is machine-generated.

This study developed Interleukin-1 receptor accessory protein (IL1RAP)-targeting chimeric antigen receptor (CAR) T cells for acute myeloid leukemia (AML). Co-administering a miR-142 mimic enhanced CAR-T cell persistence and efficacy, significantly improving survival in AML models.

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Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Interleukin-1 receptor accessory protein (IL1RAP) is highly expressed on acute myeloid leukemia (AML) cells but not normal stem cells.
  • This selective expression makes IL1RAP an attractive target for chimeric antigen receptor (CAR) T cell therapy in AML.

Purpose of the Study:

  • To develop and evaluate novel IL1RAP-targeting CAR-T cells for AML treatment.
  • To investigate strategies for enhancing CAR-T cell persistence and antileukemic activity in AML models.

Main Methods:

  • Developed IL1RAP-targeting CAR-T cells using a single-chain Fab (24scFab) with CD28 and CD3ζ domains.
  • Generated control CAR-T cells with mutated IL1RAP-binding domains.
  • Tested CAR-T cells in acute myeloid leukemia (AML) cell line-derived (CD) and patient-derived (PD) xenografts.
  • Evaluated strategies including CD3ζ ITAM mutations and co-administration of a synthetic miR-142 mimic (M-miR-142).

Main Results:

  • IL1RAP CAR-T cells showed potent antileukemic activity in AML xenograft models.
  • Mutated CAR-T cells confirmed target specificity.
  • Co-administration of M-miR-142 with IL1RAP CAR-T cells significantly increased median survival in patient-derived xenografts (78 days vs. 51 days for controls).
  • IL1RAP-1XX CAR-T cells improved in vitro persistence but not in vivo therapeutic benefit.

Conclusions:

  • IL1RAP CAR-T cell therapy is a promising approach for AML.
  • Co-administering M-miR-142 can overcome leukemia-induced immune suppression and enhance CAR-T cell efficacy.
  • This strategy offers a novel approach to improve CAR-T cell persistence and effectiveness in AML.