Targeting granzyme B to tumor cells using a yoked human chorionic gonadotropin.

ABSTRACT:

Purpose

Luteinizing hormone receptor (LHR) is found in abundance on human ovarian, breast, endometrial and prostate carcinomas but at only low levels on non-gonadal tissues. To selectively kill LHR-expressing tumors, granzyme B (GrB) was linked to a protein in which both chains of human chorionic gonadotropin were yoked together (YCG).

Methods

GrB-YCG was expressed and secreted from insect Sf9 cells. Its GrB enzymatic activity and binding affinity for hLHR were then characterized. The differential cytotoxicity of GrB-YCG versus GrB alone was tested in a panel of LHR-expressing tumor cells by SRB assay, and the mechanisms involved in the cell death were investigated by confocal fluorescence microscopy, flow cytometry, and western blot analysis.

Results

GrB-YCG was succ

SUBMITTER: Kanatani I 

PROVIDER: S-EPMC3180622 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature