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December 8, 2025Blood

Acute Myeloid Leukemia eradication targeting cathepsin g with a dual HLA-restricted TCR

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Authors

LCLuca CelliNMNeda MohammadiZMZulma Magnani

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Overview

Conducting TCR-engineered T cell therapy found significant disease eradication in AML, suggesting a favorable safety profile.

Key Points

  • This research aims to evaluate the efficacy and safety of TCR-engineered T cells targeting cathepsin g in AML.
  • Isolated CTSG-specific TCRs from healthy donors' peripheral blood mononuclear cells.
  • Evaluated T cell responses via cytokine release and degranulation marker expression.
  • Conducted TCR sequencing for tumor-specific αβ clonotypes.
  • Utilized Lentiviral vectors for transduction and CRISPR/Cas9 technology to knockout endogenous TCRs.
  • Assessed safety and activity of TCR-engineered T cells in mouse models.
  • Identified three unique CTSG-specific TCRs, with P56-TCR demonstrating dual recognition of two CTSG peptides.
  • P56-TCR redirected T cells achieved significant elimination of primary AML blasts in vitro and in vivo.
  • In vivo studies showed complete disease eradication in mice with a substantial reduction in leukemia burden (p < 0.0001).
  • CD8+ T cell population revealed potent antitumoral activity, complemented by a strong helper function from CD4+CD8+ T cells.
  • Safety assessments showed no evidence of off-target or on-target toxicities.

Cite This Study

Celli et al. (2025) studied this question.

synapsesocial.com/papers/69362f3a4fa91c937236d460https://doi.org/10.1182/blood-2025-2361
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1T cells dressed up with a dual HLA-restricted TCR targeting cathepsin G drive effective AML eradication2026 · 1 citations
  2. 2Abstract 4175: Neoantigen-guided TCR discovery pipeline to improve specificity and reduce off-target toxicity in AML2026
  3. 3Cathepsin-G specific CAR-T cells for the treatment of Acute Myeloid Leukemia 21722025
  4. 4High-avidity cathepsin-G-specific CAR-T cells for the treatment of acute myeloid leukemia.2026 · 1 citations
  5. 5A novel B7-H3-specific binder enables effective CAR T-cell therapy in an Acute Myeloid Leukemia experimental model2025