New Agents for Treatment of Recurrent Small-Cell Cancer: Tumor-Specific Abnormal Vasopressin V2 Receptor Antibodies

Abstract

We earlier demonstrated that small-cell lung cancer (SCLC) not only expresses a normal form of vasopressin V2 receptor but also an abnormal form, through alternate splicing, that lacks the seventh transmembrane region (named AbnR2). This tumor-specific abnormal receptor is expressed at the surface of cells and can be targeted by antibodies directed against a unique C-terminal region.  Immunocytochemistry reveals AbnR2 is common to all or most small-cell lung tumors. Our generated mouse monoclonal antibody was found to decrease cell viability in vitro and promote apoptotic cascades. This mouse anti-AbnR2 antibody, and a humanized form derived from it, were each found to reduce the growth of SCLC xenografts representing recurrent disease in nu/nu mice, and to have synergistic, tumor anti-proliferative effects when used with cyclophosphamide, but not cisplatin, in completely inhibiting growth. Possible mechanisms might involve normal vasopressin V2 receptors.