697

Human chorionic gonadotropin (hCG) and its β subunit are secreted by neoplastic cells in tumors of trophoblastic origin but also by various nontrophoblastic neoplasms. Furthermore, it has been reported that high level of βhCG in the serum of patients is correlated with a poor prognosis in colorectal, ovarian, prostate and bladder cancers. In addition to its interest as a tumor marker, βhCG represents an attractive anti-tumoral therapeutic target. Indeed, active immunization with either βhCG or the carboxyl terminal peptide of βhCG (CTP37) conjugated to the Diphteria Toxoid (DT-CTP37) induced tumor growth inhibition in several animal models, and clinical trials using the DT-CTP37 vaccine are in progress in colorectal and pancreatic cancer patients. In order to develop humanized antibodies targeting βhCG, a panel of tumor cell lines was screened by ELISA and quantitative RT-PCR for their capability to secrete the molecule. BxPC3, a pancreatic cell line was selected as a βhCG secreting cell line. The BxPC3 in vivo model was established and the efficacy of an anti-βhCG polyclonal serum evaluated in this model. Our results showed that compared to irrelevant polyclonal serum, anti-βhCG polyclonal serum was able to delay BxPC3 tumor growth. These results indicate that BxPC3 is a suitable model for in vivo screening of monoclonal anti-βhCG antibodies.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]