Intra-arterial administration of a replication-selective adenovirus (dl1520) in patients with colorectal carcinoma metastatic to the liver: a phase I trial

Abstract

Both replication-incompetent and replication-selective adenoviruses are being developed for the treatment of cancer and other diseases. Concerns have been raised about the safety of intra-vascular adenovirus administration following a patient death on a clinical trial with a replication-defective adenovirus. In addition, the feasibility of vascular delivery to distant tumors has been questioned. dl1520 (ONYX-015) is a replication-selective adenovirus that has previously shown safety and antitumoral activity following intratumoral injection. This is the first report of intra-vascular administration with a genetically engineered, replication-selective virus. A phase I dose-escalation trial was performed inpatients with liver-predominant gastrointestinal carcinoma (n = 11 total; primarily colorectal). dl1520 was infused into the hepatic artery at doses of 2 × 10 8 -2 × 10 12 particles for

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties

“…The HSV ICP34.5 gene counteracts the interferon-induced PKR-mediated block to virus replication, 19,20 which is usually disabled in tumour cells. ONYX-O15 has been tested in a variety of clinical situations with maximal success following repeated administration at high dose in head and neck cancer patients [21][22][23] or intra-hepatic artery infusion into liver cancer patients, 24 both combined with chemotherapy. 1716 and G207 have both been tested in glioma patients with some evidence of a slowing of the progress of the disease (1716).…”

Telomerase-dependent oncolytic adenovirus for cancer treatment

“…This strategy has been effective in animal models, and led to clinical trials combining the application of the E1B/55 kDa-deleted Onyx-015 adenovirus with chemotherapy. 5 The E1B gene, however, is also involved in the late mRNA export from the nucleus, a property that may ultimately interfere with the efficacy of the Onyx virus as a therapeutic reagent. 6,7 The second strategy involves the use of tumor-or tissue-specific promoters, such as AFP, MUC1, PSA, kallikrein-2 and pS2, to drive adenoviral genes that are essential for replication.…”

Evolving gene therapy approaches for osteosarcoma using viral vectors: Review

“…Conventional chemotherapy for OS often includes cisplatin and doxorubicin. A synergistic anti-tumor effect of CRAds with doxorubicin or cisplatin has been reported previously for other types of cancer (56,86,117,162) and CRAd therapy combined with chemotherapy has already shown promising results in solid tumors in phase I and II clinical trials (68,79,122). Furthermore, the recognition that tumor cells develop genetic mechanisms that override apoptosis caused by chemotherapy damage to their DNA dictates the finding of alternate pathways that would complement therapeutic induction of apoptosis.…”