Therapeutic efficacy of an Fc-enhanced TCR-like antibody to the intracellular WT1 oncoprotein.

ABSTRACT:

Purpose

RMFPNAPYL (RMF), a Wilms' tumor gene 1 (WT1)-derived CD8 T-cell epitope presented by HLA-A*02:01, is a validated target for T-cell-based immunotherapy. We previously reported ESK1, a high avidity (Kd < 0.2 nmol/L), fully-human monoclonal antibody (mAb) specific for the WT1 RMF peptide/HLA-A*02:01 complex, which selectively bound and killed WT1(+) and HLA-A*02:01(+) leukemia and solid tumor cell lines.

Experimental design

We engineered a second-generation mAb, ESKM, to have enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) function due to altered Fc glycosylation. ESKM was compared with native ESK1 in binding assays, in vitro ADCC assays, and mesothelioma and leukemia therapeutic models and pharmacokinetic studies in mice. ESKM toxicity was assessed in HLA

SUBMITTER: Veomett N 

PROVIDER: S-EPMC4119489 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature