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BackgroundInterleukin-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.Methods25 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.ResultsThere 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.ConclusionVaccination 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 numberISRCTN83977250.

Original publication

DOI

10.1186/1479-5876-7-2

Type

Journal article

Journal

Journal of translational medicine

Publication Date

07/01/2009

Volume

7

Addresses

Tumor Immunology Laboratory, Division of Surgical Oncology, Columbia University, New York, NY, USA. hlk2003@columbia.edu

Keywords

CD8-Positive T-Lymphocytes, Humans, Vaccinia virus, Carcinoma, Renal Cell, Kidney Neoplasms, Neoplasm Metastasis, Membrane Glycoproteins, Interleukin-2, Cancer Vaccines, Antigens, Neoplasm, Adult, Aged, Middle Aged, Female, Male, T-Lymphocytes, Regulatory, Kaplan-Meier Estimate, Biomarkers, Tumor