ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
A novel HLA-A*0201 restricted peptide derived from cathepsin G is an effective immunotherapeutic target in acute myeloid leukemia.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Phase Ib trial of folate binding protein (FBP)-derived peptide vaccines, E39 and an attenuated version, E39': An analysis of safety and immune response.Clinical immunology (Orlando, Fla.) · 2018Trial
- T-Cell Engagers in Acute Myeloid Leukemia: Molecular Targets, Structure, and Therapeutic Challenges.Cancers · 2025Review
- Article
- Shared graft-versus-leukemia minor histocompatibility antigens in DISCOVeRY-BMT.Blood advances · 2023Article
- The role of lysosomal peptidases in glioma immune escape: underlying mechanisms and therapeutic strategies.Frontiers in immunology · 2023Review
- Novel myeloperoxidase-derived HLA-A2-restricted peptides as therapeutic targets against myeloid leukemia.Cytotherapy · 2021Article
- Alkali Metal Cationization of Tumor-associated Antigen Peptides for Improved Dissociation and Measurement by Differential Ion Mobility-Mass Spectrometry.Journal of proteome research · 2020Article
- Fucosylation Enhances the Efficacy of Adoptively Transferred Antigen-Specific Cytotoxic T Lymphocytes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Computational modeling and confirmation of leukemia-associated minor histocompatibility antigens.Blood advances · 2018Article
- Targeting PR1 in myeloid leukemia.Oncotarget · 2018Article
- Cathepsin G Is Expressed by Acute Lymphoblastic Leukemia and Is a Potential Immunotherapeutic Target.Frontiers in immunology · 2017Article
- Cathepsin G is broadly expressed in acute myeloid leukemia and is an effective immunotherapeutic target.Leukemia · 2017Article
- Article
- Peptide/MHC tetramer-based sorting of CD8⁺ T cells to a leukemia antigen yields clonotypes drawn nonspecifically from an underlying restricted repertoire.Cancer immunology research · 2015Article
- Human malignant melanoma-derived progestagen-associated endometrial protein immunosuppresses T lymphocytes in vitro.PloS one · 2015Article
- Differential ion mobility spectrometry coupled to tandem mass spectrometry enables targeted leukemia antigen detection.Journal of proteome research · 2014Article
- Adoptive T-cell therapy for Leukemia.Molecular and cellular therapies · 2014Review
- Targeting cathepsin G in myeloid leukemia.Oncoimmunology · 2013Article
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19 authors.
Funding
Abstract
purposeImmunotherapy targeting aberrantly expressed leukemia-associated antigens has shown promise in the management of acute myeloid leukemia (AML). However, because of the heterogeneity and clonal evolution that is a feature of myeloid leukemia, targeting single peptide epitopes has had limited success, highlighting the need for novel antigen discovery. In this study, we characterize the role of the myeloid azurophil granule protease cathepsin G (CG) as a novel target for AML immunotherapy. EXPERIMENTAL
designWe used Immune Epitope Database and in vitro binding assays to identify immunogenic epitopes derived from CG. Flow cytometry, immunoblotting, and confocal microscopy were used to characterize the expression and processing of CG in AML patient samples, leukemia stem cells, and normal neutrophils. Cytotoxicity assays determined the susceptibility of AML to CG-specific cytotoxic T lymphocytes (CTL). Dextramer staining and cytokine flow cytometry were conducted to characterize the immune response to CG in patients.
resultsCG was highly expressed and ubiquitinated in AML blasts, and was localized outside granules in compartments that facilitate antigen presentation. We identified five HLA-A*0201 binding nonameric peptides (CG1-CG5) derived from CG, and showed immunogenicity of the highest HLA-A*0201 binding peptide, CG1. We showed killing of primary AML by CG1-CTL, but not normal bone marrow. Blocking HLA-A*0201 abrogated CG1-CTL-mediated cytotoxicity, further confirming HLA-A*0201-dependent killing. Finally, we showed functional CG1-CTLs in peripheral blood from AML patients following allogeneic stem cell transplantation.
conclusionCG is aberrantly expressed and processed in AML and is a novel immunotherapeutic target that warrants further development.
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