Re: ONYX
looking for the IMGN presentation in the thicket of AACR presentations, I found this re ONXX:
520 Activity of ONYX-015 in combination with chemotherapeutic agents against human tumor cells lines. Davidson Karen1, Cerna Cesaer1, Lawrence Richard A.1, Von Hoff Daniel D1, Kirn David2, Heise Carla2, Izbicka Elzbieta1. 1Institute for Drug Development, CTRC, San Antonio TX and 2Onyx Pharmaceuticals, Richmond, CA.
An attenuated adenovirus ONYX-015 destroys tumor cells lacking a functional p53 gene. We tested ONYX-015 in combination with standard chemotherapeutic agents to determine the effect of the combination on virus replication, cell growth, and apoptosis in four human tumor cell lines: two colon carcinomas with different p53 expression status, three ovarian carcinomas differing in sensitivity to chemotherapy, a pancreatic carcinoma with a mutated p53, and a head and neck carcinoma with a non-functional p53. The studies were performed at predetermined time points in cells infected with the virus. ONYX-015 induced cytopathic effects in p53-deficient cell lines at low concentration (0.01 pfu/cell). At 10 pfu/cell, ONYX-015 induced apoptosis in p53 wild-type and p53-deficient colon cancer cell lines. In the parent drug-sensitive ovarian carcinoma, ONYX-015 infection significantly increased apoptosis. Apoptosis was also increased in adriamycin- or cisplatin-resistant ovarian carcinoma lines at lower concentrations of ONYX-015 compared to the parent cell line. In adriamycin- or cisplatin-resistant ovarian carcinomas, the chemotherapeutic agents had no effect on apoptosis, while the combination of the drugs and ONYX-015 increased apoptosis more than ONYX-015 alone. Apoptosis was only moderately increased in a pancreatic carcinoma infected by ONYX-015, but the drug combination was more effective. The head and neck carcinoma cells were very resistant to apoptosis induction, and co-infection with chemotherapeutic agents and ONYX-015 did not further increase apoptosis. In all cancer cell lines responsive to the virus, the combination of chemotherapeutic agents plus ONYX-015 increased the level of apoptosis compared to chemotherapy alone. ONYX-015 infection apparently reversed the resistance to adriamycin and cisplatin in ovarian cancer cell lines. The results of this study warrant future clinical trials that include combination studies, especially in drug resistant ovarian tumors.
Supported by Onyx Pharmaceuticals |
