Immune stimulatory effect of anti-EpCAM immunotoxin–improved overall survival of metastatic colorectal cancer patients

Abstract

Introduction: In a recent phase I trial in a heterogeneous group of carcinoma patients with advanced disease, we did not observe objective responses by CT at 8 weeks in patients treated with either the anti-EpCAM immunotoxin MOC31PE alone or administered in combination with the immunosuppressor cyclosporin (CsA). We have now assessed overall survival (OS) data for the two groups to reveal potential differences, and to elucidate putative underlying mechanisms. Material and methods: The OS time of MOC31PE monotherapy (34 patients) and MOC31PE in combination with CsA (23 patients), was assessed. Pre- and post-treatment patient sera were analyzed in a multiplex immunoassay, and the immunogenic effects of MOC31PE were studied in vitro and in a dendritic cell maturation assay. Results: When the data were analyzed for all treated patients regardless of cancer type, the MOC31PE alone group had a median OS of 12.7 months (95% CI = 5.6–19.8 months) compared to 6.2 months (95% CI = 5.6–6.8 months) (p=.066) for the patients treated with MOC31PE + CsA group. For the subgroup of patients with colorectal cancer, the median OS survival was 16.3 months (95% CI = 5.6–27.0) for the MOC31PE only cohort (n = 15), compared to 6.0 months (CI = 5.8–6.2) (p