A monoclonal antibody targeting melanoma-associated chondroitin sulfate proteoglycan demonstrates antitumor activity in human melanoma, ovarian and breast cancer models.

B40 Melanoma-associated chondroitin sulfate proteoglycan (MCSP) is a glycoprotein-proteoglycan complex present on the surface of melanoma cells, and has been reported to have a role in cancer progression by enhancing adhesion and invasion of melanoma cells through multiple mechanisms. MCSP, also known as the high molecular weight-melanoma associated antigen (HMW-MAA), has been shown recently to be expressed in human breast cancer stem cells.
 AR11BD-2E11-2, a monoclonal antibody that targets MCSP was discovered using the FunctionFIRST™ platform. Briefly, human breast cancer tissue was used to immunize mice and hybridomas were screened for cytotoxicity against a variety of cancer cell lines. For example, AR11BD-2E11-2 showed cytotoxicity in breast and ovarian cancer cell lines. When AR11BD-2E11-2 was evaluated in vivo, anti-tumor activity was apparent not only in breast and ovarian tumor models, but in a model of human melanoma as well. In the MCF-7 xenograft breast cancer model, AR11BD-2E11-2 was shown to significantly reduce tumor volume by 79% compared to isotype control treated mice (p=0.048), as well as confer a significant survival benefit (p=0.03). A 49% (p=0.0004) reduction in tumor volume was also observed in a second breast cancer xenograft model MDA-MB-231. In an OVCAR-3 xenograft ovarian cancer model, the increase in body weight due to ascites can be used as a marker of disease progression. In this model, the mice in the control treated group showed a 60% tumor-related weight gain, while the AR11BD-2E11-2 treated mice showed a significantly lower weight gain of 40% (p=0.03) corresponding to decreased ascites formation, as well as having a significantly longer mean survival time (p