| Autor: |
Mitcham Josephine, DeRaffele Gail, Moroziewicz Dorota, Shingler William H, Kim Dae, Sherman William, Taback Bret, Kaufman Howard L, Carroll Miles W, Harrop Richard, Naylor Stuart, Kim-Schulze Seunghee |
| Jazyk: |
angličtina |
| Rok vydání: |
2009 |
| Předmět: |
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| Zdroj: |
Journal of Translational Medicine, Vol 7, Iss 1, p 2 (2009) |
| Druh dokumentu: |
article |
| ISSN: |
1479-5876 |
| DOI: |
10.1186/1479-5876-7-2 |
| Popis: |
Abstract Background Interleukin-2 (IL-2) induces durable objective responses in a small cohort of patients with metastatic renal cell carcinoma (RCC) but the antigen(s) responsible for tumor rejection are not known. 5T4 is a non-secreted membrane glycoprotein expressed on clear cell and papillary RCCs. A modified vaccinia virus Ankara (MVA) encoding 5T4 was tested in combination with high-dose IL-2 to determine the safety, objective response rate and effect on humoral and cell-mediated immunity. Methods 25 patients with metastatic RCC who qualified for IL-2 were eligible and received three immunizations every three weeks followed by IL-2 (600,000 IU/kg) after the second and third vaccinations. Blood was collected for analysis of humoral, effector and regulatory T cell responses. Results There were no serious vaccine-related adverse events. While no objective responses were observed, three patients (12%) were rendered disease-free after nephrectomy or resection of residual metastatic disease. Twelve patients (48%) had stable disease which was associated with improved median overall survival compared to patients with progressive disease (not reached vs. 28 months, p = 0.0261). All patients developed 5T4-specific antibody responses and 13 patients had an increase in 5T4-specific T cell responses. Although the baseline frequency of Tregs was elevated in all patients, those with stable disease showed a trend toward increased effector CD8+ T cells and a decrease in Tregs. Conclusion Vaccination with MVA-5T4 did not improve objective response rates of IL-2 therapy but did result in stable disease associated with an increase in the ratio of 5T4-specific effector to regulatory T cells in selected patients. Trial registration number ISRCTN83977250 |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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