gms | German Medical Science

Introduction: EpCAM functions as an epithelial cell adhesion molecule with a potential role in tumorigenesis such as suppression of cadherin-mediated cellular adhesion promoting cancer cell invasion and metastasis. Recently, the fully human monoclonal antibody MT-201 targeting an extracellular epitope of EpCAM was developed for clinical use. It was the aim of our study to elucidate the role of EpCAM in PCA progression by immunohistochemical (IHC) analysis and evaluation of MT-201 cytotoxicity in PCA cell lines.

Material and Methods: Paraffinized tissue sections of 70 radical prostatectomy specimens (pT2a-4, pN1, Gleason ≤6, 7, 8-10) were incubated with an anti-EpCAM mAb and counterstained with the avidin/biotin method. Expression analysis was done via a semiquantitative 12-score system equivalent to the Rimmele-score used for c-erb analysis in breast cancer. Antibody-dependent cellular cytoxicity (ADCC) induced by MT-201 was tested in EpCam positive cell lines Kato III, HT29, LNCaP, in EpCam negative cell lines DU145, PC3 and in primary human PCA cell lines extracted from PCA obtained at time of surgery. Lysis of cell lines was analysed and quantified by FACS

Results:IHC homogenous EpCAM expression was shown in 96% of PCA samples [mean score of 10.2 (8-12)]; pT1/2 & pT3 PCA showed a homogenous expression in 80% & 90%, resp.. pT4 and pN1 PCA demonstrated significantly lower scores of 7.57±1.68 and 9.79±1.32, resp. (p = 0.01). There was no significant difference in expression profiles between different Gleason scores. In-vitro studies showed that MT-201 induced ADCC in EpCAM positive cancer cell lines but not in EpCAM negative cell lines; also MT201 was able to kill primary human PCA cells in the presence of autologous effector cells derived from the same tumor tissue sample. No significant lysis was induced by equivalent concentrations of the human IgG1 antibody Rituximab demonstrating specificity of MT201.

Discussion: IHC and in-vitro studies demonstrate the potential therapeutic options of MT201 in patients with progressive PCA. A prospective randomized placebo-controlled clinical phase-II trial in men with PSA progression following RRP has been completed and data are currently analysed.