ArticleBlood2011
An anti-PR1/HLA-A2 T-cell receptor-like antibody mediates complement-dependent cytotoxicity against acute myeloid leukemia progenitor cells.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 117 citations in OpenAlex.
- Trial
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- Next-generation immunotherapeutic approaches for blood cancers: Exploring the efficacy of CAR-T and cancer vaccines.Experimental hematology & oncology · 2025Review
- Migrasomes as intercellular messengers: potential in the pathological mechanism, diagnosis and treatment of clinical diseases.Journal of nanobiotechnology · 2025Review
- Article
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- Hu8F4-CAR T cells with mutated Fc spacer segment improve target-specificity and mediate anti-leukemia activityResearch square · 2024Article
- Harnessing antibody-mediated recognition of the intracellular proteome with T cell receptor-like specificity.Frontiers in immunology · 2024Review
- Challenges and solutions for therapeutic TCR-based agents.Immunological reviews · 2023Review
- A modified SELEX approach to identify DNA aptamers with binding specificity to the major histocompatibility complex presenting ovalbumin model antigen.RSC advances · 2023Article
- The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based Immunotherapy.Cells · 2022Review
- Evaluation of chimeric antigen receptor of humanized rabbit-derived T cell receptor-like antibody.Cancer science · 2022Article
- Emerging CAR T Cell Strategies for the Treatment of AML.Cancers · 2022Review
- Targets for chimeric antigen receptor T-cell therapy of acute myeloid leukemia.Frontiers in immunology · 2022Review
- Identification of CD8Frontiers in immunology · 2022Article
- Monoclonal Antibodies Generation: Updates and Protocols on Hybridoma Technology.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Review
- TARP as antigen in cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2021Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
PR1 (VLQELNVTV) is a human leukocyte antigen-A2 (HLA-A2)-restricted leukemia-associated peptide from proteinase 3 (P3) and neutrophil elastase (NE) that is recognized by PR1-specific cytotoxic T lymphocytes that contribute to cytogenetic remission of acute myeloid leukemia (AML). We report a novel T-cell receptor (TCR)-like immunoglobulin G2a (IgG2a) antibody (8F4) with high specific binding affinity (dissociation constant [K(D)] = 9.9nM) for a combined epitope of the PR1/HLA-A2 complex. Flow cytometry and confocal microscopy of 8F4-labeled cells showed significantly higher PR1/HLA-A2 expression on AML blasts compared with normal leukocytes (P = .046). 8F4 mediated complement-dependent cytolysis of AML blasts and Lin(-)CD34(+)CD38(-) leukemia stem cells (LSCs) but not normal leukocytes (P < .005). Although PR1 expression was similar on LSCs and hematopoietic stem cells, 8F4 inhibited AML progenitor cell growth, but not normal colony-forming units from healthy donors (P < .05). This study shows that 8F4, a novel TCR-like antibody, binds to a conformational epitope of the PR1/HLA-A2 complex on the cell surface and mediates specific lysis of AML, including LSCs. Therefore, this antibody warrants further study as a novel approach to targeting leukemia-initiating cells in patients with AML.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.