Of 22 patients with liver tumours who were assessed for eligibility, eight patients did not meet inclusion criteria. Therefore, 14 patients, including those with hepatocellular, colorectal, melanoma, and lung cancer, were enrolled. Patients were heavily pretreated (5·6 previous treatments, SD 2·8, range 2·0–12·0) and had large tumours (7·0 cm diameter, SD 2·7, range 1·8–10·9). Patients received a mean of 3·4 (SD 2·2, range 1·0–8·0) cycles of JX-594. All patients were evaluable for toxicity. All patients experienced grade I–III flu-like symptoms, and four had transient grade I–III dose-related thrombocytopenia. Grade III hyperbilirubinaemia was dose-limiting in both patients at the highest dose; the MTD was therefore 1×109 pfu. JX-594 replication-dependent dissemination in blood was shown, with resultant infection of non-injected tumour sites. GM-CSF expression resulted in grade I–III increases in neutrophil counts in four of six patients at the MTD. Tumour responses were shown in injected and non-injected tumours. Ten patients were radiographically evaluable for objective responses; non-evaluable patients had contraindications to contrast medium (n=2) or no post-treatment scans (n=2). According to Response Evaluation Criteria in Solid Tumors (RECIST), three patients had partial response, six had stable disease, and one had progressive disease.
Intratumoral injection of JX-594 into primary or metastatic liver tumours was generally well-tolerated. Direct hyperbilirubinaemia was the dose-limiting toxicity. Safety was acceptable in the context of JX-594 replication, GM-CSF expression, systemic dissemination, and JX-594 had anti-tumoral effects against several refractory carcinomas. Phase II trials are now underway.
Jennerex Biotherapeutics (San Francisco, CA, USA) and Green Cross Corporation (Giheung-Gu, Yongin, South Korea).
Oncolytic biotherapy: a novel therapeutic platform The Lancet Oncology |
Oncolytic biotherapy: a novel therapeutic platform The Lancet Oncology, Volume 3, Issue 1, January 2002, Pages 17-26 Lynda K Hawkins, Nick R Lemoine, David Kirn Abstract SummaryThere is a clear need for new, selective, cancer treatments that do not cause the cross-resistance which occurs with currently available chemotherapeutic agents. Gene therapy is a promising approach, but to date, it has shown limited effectiveness in clinical trials because of insufficient gene transduction. Many investigators are now revisiting the ‘old’ idea of using tumour-specific, replication-selective viruses or bacteria to treat cancer. These agents can be directly oncolytic, but can also be used to simultaneously express therapeutic genes in target cells or induce tumour-specific, cellmediated immunity. We discuss the promise of this rapidly evolving field and examine the potential barriers to its success.Purchase PDF (567 K) |
In Situ Immune Modulation Using Recombinant Vaccinia Virus Vectors: Preclinical Studies to Clinical Implementation Gene Therapy of Cancer (Second Edition), 2002, Pages 207-223 Edmund C. Lattime, Laurence C. Eisenlohr, Leonard G. Gomella, Michael J. Mastrangelo |
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