ONYX-015

[armin.b]

Aus einer Zeitung habe ich etwas über das Medikament(?) ONYX-015 erfahren. Dieses soll in zusammenhang mit einer Chemotherapie eine gute Ansprechrate bei der Krebstherapie sein. Gibt irgendwo weiter Informationen in Deutschland darüber. ONYX-015 kommt wohl aus den USA. Die einzigen Informationen über ONYX-015, welche ich gefunden habe, bezogen sich auf klinische Studien.

[Prof. Wust]

RE: ONYX-015


Es handelt sich um einen Adeno-Virus (s.u.). Es ist eine hochexperimentelle Therapie, die gerade mal in der Phase I derzeit in klinischen Studien geprüft wird (also nur Prüfung der Verträglichkeit, noch keine Effektivität). Es wirkt nur bei bestimmten Tumoren mit p53 Defekten. Von einer gesicherten klinischen Anwendung ist man weit entfernt (siehe dazu die beiliegenden Zu-sammenfassungen aus neuesten Zeitschriften)

Viruses as antitumor weapons: defining conditions for tumor remission.
AU: Wodarz,-D
AD: Institute for Advanced Study, Einstein Drive, Princeton, New Jersey 08540. [email protected]
SO: Cancer-Res. 2001 Apr 15; 61(8): 3501-7
AB: Recent research has indicated that viruses specifically infecting tumor cells could be used as an alternative therapeutic approach in cancer patients. A particular example is the adenovirus ONYX-015, which has entered clinical trials in the context of head and neck cancer. Successful therapy crucially requires an understanding about how viral and host parameters influence tumor load. The interactions between the growing tumor, the replicating virus, and possible immune responses are multifactorial and nonlinear. Hence, a complete understanding of how virus and host characteristics influence the outcome of therapy requires mathematical models. In this study, such mathematical models are presented and analyzed. The study investigates three possible scenarios that could be relevant for therapy: (a) Viral cytotoxicity alone kills tumor cells; (b) a virus-specific lytic CTL response contributes to killing of infected tumor cells; (c) the virus elicits immunostimulatory signals within the tumor that promote the development of tumor-specific CTL. The models precisely define conditions required for successful therapy. They identify the para-meters that need to be measured and modulated to evaluate and refine the existing therapy re-gimes.

Safety and feasibility of injection with an E1B-55 kDa Gene-deleted, replication-selective adeno-virus (ONYX-015) into primary carcinomas of the pancreas: a phase I trial.
AU: Mulvihill,-S; Warren,-R; Venook,-A; Adler,-A; Randlev,-B; Heise,-C; Kirn,-D
AD: University of California, San Francisco, Department of Surgery, USA.
SO: Gene-Ther. 2001 Feb; 8(4): 308-15
AB: Novel therapies are needed for locally advanced pancreatic carcinoma. ONYX-015 (dl1520) is an E1B-55 kDa region-deleted adenovirus that selectively replicates in and lyses tumor cells with abnormalities in p53 function (eg gene mutation). We carried out a phase I dose escalation study of ONYX-015 in patients with unresectable pancreatic cancer. ONYX-015 was administe-red via CT-guided injection (n = 22 patients) or intraoperative injection (n = 1) into pancreatic primary tumors every 4 weeks until tumor progression. Interpatient dose escalation was carried out with at least three patients per dose level from 10(8) p.f.u. up to the 10(11) p.f.u. dose level (two patients treated at this dose). The majority of patients had abnormally low cellular immunity (CD4 counts and hypersensitivity skin testing). Injection of ONYX-015 into pancreatic carcinomas was well-tolerated. Mild, transient pancreatitis was noted in only one patient. Dose-escalation proceeded to the highest dose level. Neutralizing antibodies rose post-treatment in all patients. After injection, ONYX-015 was detectable in the blood 15 min later, but not between 1 and 15 days later. Viral replication was not documented, however, in contrast to trials in other tumor types. No objective responses were demonstrated. Intratumoral injection of an E1B-55 kDa region-deleted adenovirus into primary pancreatic tumors was feasible and well-tolerated at doses up to 10(11) p.f.u. (2 x 10(12) particles), but viral replication was not detectable.