Physicians attending the annual meeting of the American Society of Clinical Oncology (ASCO) presented evidence that pegylated arginine deiminase (ADI-PEG 20), a novel anticancer drug that targets ASS(-) tumors, and which is being developed and manufactured by Polaris Group, was effective in inhibiting the growth of metastatic melanoma cells. Dr. L.G. Feun from the University of Miami, Miami, FL presented results from a phase II trial in 36 metastatic melanoma patients who were treated with ADI-PEG 20 weekly by intramuscular injection and who were evaluable for response. Of the evaluable patients, 14/36 (39%) had a tumor response and/or clinical benefit. For 16 patients with ASS(-) tumors, 10/16 (63%) showed some evidence of antitumor effect, while only 1/10 (10%) patients had stable disease when the tumor was ASS(+). Polaris plans to initiate its first phase III clinical trial with ADI-PEG 20 during 4Q 2010 in treating hepatocellular carcinoma which has a high prevalence of ASS(-) tumor cells.
A second study presented at the ASCO meeting by Dr. P.W. Szlosarek from Barts Cancer Research UK Centre and colleagues from other UK medical centers, assessed ASS expression in normal and malignant lymphoid cell lines and tissues. Using several detection methods and malignant and normal cell lines, a good correlation was observed with absence of ASS in tumor cells but not in normal cells. Notably, ASS protein was absent in >99% of lymphoma cells as assessed by immunohistochemical staining. When these cell lines were treated with ADI-PEG 20, the ASS(-) malignant lymphoma cells displayed apoptotic effects and were inhibited in growth while the normal lymphoblastoid ASS(+) cell lines and those in which ASS could be induced, were resistant to the apoptotic effects of ADI-PEG 20. “ASS(-) lymphomas are sensitive to arginine depletion suggesting that this approach is worth exploring as a potential novel therapeutic approach in the management of patients with lymphoma,” said Dr. Szlosarek.
ASS is required for the production of arginine, an amino acid needed for growth and replication of cells. Normal tissue cells have normal levels of ASS and can produce sufficient arginine for their own growth and survival in the presence of ADI-PEG 20. However, growth and replication of ASS-deficient tumor cells is inhibited by ADI-PEG 20. This inhibition occurs because ADI-PEG 20 breaks down the circulating arginine that ASS-deficient tumor cells rely upon. The studies presented at this year’s annual ASCO meeting provide convincing evidence that ADI-PEG 20 can inhibit growth of metastatic melanoma cells and lymphomas along with other tumor types that have been reported at other cancer meetings and in scientific publications. Clinical studies in other human cancers such as small cell lung cancer, mesothelioma, sarcoma and leukemia are planned to begin in the near future.