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February 12, 2025LeukemiaOpen Access

Immunotherapy targeting a leader sequence cathepsin G-derived peptide

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Authors

CSChunhua ShiZTZe TianJYJun Yan

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Overview

Preclinical study demonstrates selective leukemic cytotoxicity by a novel bispecific T-cell engager in acute myeloid leukemia, supporting its clinical progression.

Key Points

  • To engineer and evaluate the preclinical antitumor efficacy and safety profile of a bispecific T-cell engager targeting the leader sequence-derived cathepsin G peptide CG1 presented by HLA-A2.
  • Engineered a T-cell receptor-mimic bispecific antibody (CG1/A2xCD3) designed to bind the CG1/HLA-A2 complex and CD3.
  • Evaluated binding affinity, T-cell activation, and cytotoxic efficacy against HLA-A2+ acute myeloid leukemia cell lines and primary patient blasts in vitro and in vivo.
  • Assessed off-target cytotoxic activity using healthy human bone marrow samples.
  • CG1/A2xCD3 demonstrated high binding affinity to CG1/HLA-A2 complexes and stimulated potent cytotoxic killing of HLA-A2+ primary leukemia blasts and cell lines both in vitro and in vivo.
  • Tumor cell destruction correlated with target-dependent T-cell activation and robust cytokine secretion.
  • The bispecific antibody exhibited no cytotoxic activity against normal bone marrow cells.

Cite This Study

Shi et al. (2025) studied this question.

synapsesocial.com/papers/6a105d62d478ddac0ffcc7dbhttps://doi.org/10.1038/s41375-025-02520-x
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Also Consider

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

  1. 1Cathepsin-G specific CAR-T cells for the treatment of Acute Myeloid Leukemia 21722025
  2. 2High-avidity cathepsin-G-specific CAR-T cells for the treatment of acute myeloid leukemia.2026 · 1 citations
  3. 3Abstract 1236: Characterization of CBX-250, a first-in-class TCR-mimetic-based T-cell engager targeting a cathepsin G peptide-HLA complex for the treatment of myeloid leukemia2024 · 1 citations
  4. 4T cells dressed up with a dual HLA-restricted TCR targeting cathepsin G drive effective AML eradication2026 · 1 citations
  5. 5Acute Myeloid Leukemia eradication targeting cathepsin g with a dual HLA-restricted TCR2025