Abstract 4579: CSPG4 monoclonal antibodies inhibit the growth of human malignant mesothelioma

Abstract Malignant Mesothelioma (MM) is a very aggressive cancer, resistant to current chemotherapy, with a median survival of 1 year from diagnosis. The membrane bound Chondroitin Sulphate Proteoglycan 4 (CSPG4) is involved in tumor onset and progression, as well as in angiogenesis. Because of high expression on the surface of cancer cells, CSPG4 represents an attractive target for immunotherapy. CSPG4 was detected in 24 out of 40 MM biopsies, with minimal expression on surrounding normal cells. CSPG4 expression in MM cells was induced upon engagement on extracellular matrix components (ECM). Cell attachment and survival was greater to fibronectin than other ECM. Therefore, we aimed at using CSPG4 monoclonal antibodies (mAb) to impair MM growth. CSPG4-specific TP41.2 mAb inhibited MM cell attachment to ECM, the resulting intracellular signaling and cell survival, with a two-fold increase in apoptosis, compared to isotype IgG control treated cells. Moreover, interfering with the function of CSPG4 by TP41.2 significantly reduced MM cell motility, invasiveness and wound healing. CSPG4 is involved also in the maintenance of the transformed phenotype, as assessed by anchorage-independent growth assay. A significant reduction in soft-agar colony size and numbers was observed when MM cells were treated with TP41.2, compared to control cells. Preliminary studies of in vivo tumorigenesis, performed on SCID mice xenografts, reveal that TP41.2 mAb is able to either prevent MM tumor establishment or reduce tumor mass volume. Our results strongly suggest that CSPG4 mAb-based immunotherapy may represent a novel valid approach for the treatment of MM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4579. doi:10.1158/1538-7445.AM2011-4579