Related Experiment Video

Updated: Sep 20, 2025

A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
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A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells

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T cell receptor mimic CAR T cells targeting cathepsin G signal peptide

Jun Yan1, Chunhua Shi1, Guojun Yang1

  • 1Oncology Research for Biologics and Immunotherapy Translation (ORBIT), University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Leukemia
|May 28, 2025
PubMed

Insights

Researchers identified a novel immunotherapy target, CG1, for myeloid leukemias like acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). CG1-targeting chimeric antigen receptor (CAR) T cells show potent anti-leukemia activity without harming normal blood cells.

Area of Science:

  • Immunology
  • Oncology
  • Hematology

Background:

  • Limited immunotherapy targets exist for myeloid malignancies.
  • Signal peptides represent a novel class of potential immunotherapeutic targets.

Purpose of the Study:

  • To engineer and evaluate chimeric antigen receptor (CAR) T cells targeting the HLA-A2-restricted, cathepsin G-derived signal peptide (CG1) for myeloid leukemias.
  • To assess the preclinical efficacy and safety of CG1/A2-CAR T cells in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML).

Main Methods:

  • Development of CG1/A2-targeting CAR T cells utilizing T cell receptor-mimic (TCR-m) constructs.
  • Assessment of CG1/A2 TCR-m affinity for CG1/A2 monomers and leukemia cells.
  • In vitro and in vivo evaluation of CG1/A2-CAR T cell efficacy against HLA-A2+ AML and CML.
  • Analysis of CG1/A2-CAR T cell impact on normal bone marrow hematopoiesis.

Main Results:

  • CG1/A2 TCR-m demonstrated high affinity for CG1/A2 and CG1/A2-expressing AML and CML cells.
  • CG1/A2-CAR T cells exhibited potent killing of HLA-A2+ AML and CML in vitro and in vivo.
  • CG1/A2-CAR T cells did not adversely affect normal bone marrow hematopoiesis.

Conclusions:

  • Signal peptides, such as CG1, are validated as viable immunotherapeutic targets in myeloid malignancies.
  • CG1/A2-CAR T cells demonstrate promising preclinical efficacy and safety, supporting further clinical development for AML and CML treatment.

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