Toxicity Assessment of Intratumoral Injection of the Herpes Simplex Type I Thymidine Kinase Gene Delivered by Retrovirus in Patients with Refractory Cancer
| Autor: | Casey Cunningham, Angela Buchanan, Doug Jolly, Sandeep Singh, John Nemunaitis |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Ganciclovir viruses Genetic Vectors Herpesvirus 1 Human Transfection Antiviral Agents Thymidine Kinase Injections Breast cancer Neoplasms Drug Discovery medicine Genetics Animals Humans Refractory Carcinoma Lung cancer Molecular Biology Aged Aged 80 and over Pharmacology business.industry Melanoma Gene Transfer Techniques Cancer Genetic Therapy Middle Aged medicine.disease Retroviridae Thymidine kinase Immunology Cancer research Molecular Medicine Female Sarcoma Neoplasm Recurrence Local business medicine.drug |
| Zdroj: | Molecular Therapy. 4(2):157-160 |
| ISSN: | 1525-0016 |
| DOI: | 10.1006/mthe.2001.0430 |
| Popis: | Introduction of the herpes simplex type I thymidine kinase ( HSV-TK ) gene into tumor tissue, followed by ganciclovir, initiates a phosphorylation cascade that induces formation of a toxic ganciclovir triphosphate. Animal trials suggest that this ganciclovir triphosphate has antitumor activity. Here we report application of the HSV-TK transfection approach using a retroviral construct. Sixteen patients (median age 61.5 years) with refractory carcinoma (13 melanoma, 1 breast cancer, 1 nonsmall-cell lung cancer, and 1 osteogenic sarcoma) received intratumoral injection of HSV-TK retroviral vector at escalating doses (0.2×10 7 cfu per injection ×5 daily doses) and we evaluated them for toxicity and activity. We observed grade III pain associated with cellulitis in one patient following injection. Analysis of blood samples drawn between 3 and 28 weeks from 14 patients for replication-competent retrovirus by PCR analysis of the amphotrophic envelope revealed no replication-competent retrovirus. We injected 21 lesions. We identified no tumor responses of the injected lesions. Of 13 patients with advanced melanoma, 6 survived over one year. Thus, injection of retroviral delivered HSV-TK in patients with refractory cancer was well-tolerated. |
| Databáze: | OpenAIRE |
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