Approximately 90% of renal cell
tumors overexpress the
tumor antigen 5T4. The attenuated strain of vaccinia virus, modified
vaccinia Ankara, has been engineered to express 5T4 (
TroVax). We conducted an open-label phase 1/2 trial in which
TroVax was administered alongside
interferon-alpha (IFNalpha) to 11 patients with metastatic
renal cell carcinoma.
Antigen-specific cellular and humoral responses were monitored throughout the study, and clinical responses were assessed by measuring the changes in
tumor burden by computed tomography scan (Response Evaluation Criteria In Solid Tumors). The primary objective was to assess the safety, immunogenicity, and efficacy of
TroVax when given alongside IFNalpha. Treatment with
TroVax plus IFNalpha was well tolerated with no serious adverse events attributed to
TroVax. All 11 patients mounted 5T4-specific antibody responses and 5 (45%) mounted cellular responses. No objective
tumor responses were seen, but the overall median time to progression (
TTP) of 9 months (range: 2.1 to 26+ mo) was longer than expected for IFNalpha alone. For the 10 clear cell patients the
TTP ranged from 3.9 to 26+ months, with a median
TTP of 10.4 months. The high frequency of 5T4-specific immune responses and prolonged median
TTP for clear cell patients compared with that expected for IFNalpha alone is encouraging and warrants further investigation.