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Ref Type Journal Article
PMID (27055866)
Authors Sergeeva A, He H, Ruisaard K, St John L, Alatrash G, Clise-Dwyer K, Li D, Patenia R, Hong R, Sukhumalchandra P, You MJ, Gagea M, Ma Q, Molldrem JJ
Title Activity of 8F4, a T-cell receptor-like anti-PR1/HLA-A2 antibody, against primary human AML in vivo.
Journal Vol Issue Date Pages Journal Short Title
Leukemia 30 7 2016 07 1475-84 Leukemia
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Hu8F4 Hu8F4 0 1
Drug Name Trade Name Synonyms Drug Classes Drug Description
Hu8F4 Hu8F4 is a monoclonal antibody against the HLA-A2 restricted 9-mer peptide PR1, which may induce cytotoxic immune response against leukemia cells (PMID: 27055866).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References