Abstract
The PR1 peptide, derived from the leukemia-associated antigens proteinase 3 and neutrophil elastase, is overexpressed on HLA-A2 in acute myeloid leukemia (AML). We developed a high-affinity T-cell receptor-like murine monoclonal antibody, 8F4, that binds to the PR1/HLA-A2 complex, mediates lysis of AML and inhibits leukemia colony formation. Here, we explored whether 8F4 was active in vivo against chemotherapy-resistant AML, including secondary AML. In a screening model, coincubation of AML with 8F4 ex vivo prevented engraftment of all tested AML subtypes in immunodeficient NSG (NOD scid IL-2 receptor γ-chain knockout) mice. In a treatment model of established human AML, administration of 8F4 significantly reduced or eliminated AML xenografts and extended survival compared with isotype antibody-treated mice. Moreover, in secondary transfer experiments, mice inoculated with bone marrow from 8F4-treated mice showed no evidence of AML engraftment, supporting the possible activity of 8F4 against the subset of AML with self-renewing potential. Our data provide evidence that 8F4 antibody is highly active in AML, including chemotherapy-resistant disease, supporting its potential use as a therapeutic agent in patients with AML.
Original language | English (US) |
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Pages (from-to) | 1475-1484 |
Number of pages | 10 |
Journal | Leukemia |
Volume | 30 |
Issue number | 7 |
DOIs | |
State | Published - Jul 1 2016 |
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research
MD Anderson CCSG core facilities
- Monoclonal Antibody Facility
- Flow Cytometry and Cellular Imaging Facility
- Research Animal Support Facility
- Tissue Biospecimen and Pathology Resource