Fully human antagonistic antibodies against CCR4 potently inhibit cell signaling and chemotaxis.

ABSTRACT:

Background

CC chemokine receptor 4 (CCR4) represents a potentially important target for cancer immunotherapy due to its expression on tumor infiltrating immune cells including regulatory T cells (Tregs) and on tumor cells in several cancer types and its role in metastasis.

Methodology

Using phage display, human antibody library, affinity maturation and a cell-based antibody selection strategy, the antibody variants against human CCR4 were generated. These antibodies effectively competed with ligand binding, were able to block ligand-induced signaling and cell migration, and demonstrated efficient killing of CCR4-positive tumor cells via ADCC and phagocytosis. In a mouse model of human T-cell lymphoma, significant survival benefit was demonstrated for animals treated with the

SUBMITTER: Hagemann UB 

PROVIDER: S-EPMC4117600 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature