Abstract B235: The utility of TRC093; A humanized monoclonal antibody directed against cleaved collagen in the detection of patients at risk of ovarian and breast cancer
Authors: Liebes Leonard , Lu Jennifer , Pennell Ryan , Blank Stephanie , Pua Tarah , Muggia Franco , Fishman David , Theuer Charles , Roth Jenn , Brooks Peter 
Published: June 2012

Background: TRC093 is a humanized monoclonal antibody that specifically binds cleaved collagen and has been shown to inhibit angiogenesis and tumor growth in preclinical studies. TRC093 is currently being evaluated in a phase I clinical study for the treatment of metastatic human tumors (Gordon et al. EJC Supp 6, abs #414, pp130, 2008). Interestingly, one of the patients in this study with granulosa cell carcinoma of the ovary with progressive disease had a mixed response in the liver after 2 months of treatment. Given these encouraging results, we began to examine the biological relevance of the cryptic epitope recognized by TRC093 in ovarian carcinoma and whether a soluble form of this cryptic collagen epitope may represent a clinically useful marker for patients at risk for ovarian and breast cancer. To this end, we have adapted an ELISA assay for the detection of the shed collagen cryptic epitope that is defined by this antibody to examine a patient population at risk for ovarian and breast cancer.

Methods: To begin to assess the relevance of the cryptic collagen epitope recognized by TRC093 in ovarian tumor growth, human SKOV3 ovarian carcinoma cells were injected subcutaneously into nude mice. Six days later when detectable tumors were observed, mice were treated (i.p.) 3x per week with TRC093 over a dose range up to 250 µg/injection for a period of 28 days. To assess the relevance of a shed soluble form of the cryptic collagen epitope in a patient population at risk for ovarian and breast cancer, serum samples from a group of high-risk women volunteers prospectively enrolled at the NYU School of Medicine were analyzed for TRC093 epitope concentration by ELISA as previously described (Ng et al., Clin Can Res, 14:6253).

Results: TRC093 significantly (p&lt; 0.05) inhibited SKOV3 tumor growth at 100 µg and 250 µg/injection as compared to control. These findings suggest that theTRC093 cryptic collagen epitope may represent a relevant therapeutic target for ovarian carcinoma. In a group of 23 high-risk women identified with respect to their clinical status, a mean ± SEM of 42.9 ± 9.8 µg/ml was determined for the patients with ovarian/ breast cancer history compared with a mean of 15.3 ± 2.9 µg/ml for normal women in this study population (p = 0.0254).

Conclusions: The TRC093 shed serum epitope can distinguish between a high-risk population of women with breast or ovarian cancer and normal clinical status. We are expanding the sample size with more ovarian surgical patients. The xenograft studies provide further support for the potential use of the SKOV3 human ovarian carcinoma model to examine the effect of TRC093 in combination with cisplatin and or bevacizumab. The TRC093 epitope may represent a key therapeutic target in ovarian cancer.

Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B235.