Abstract |
Attenuated vaccinia virus, modified vaccinia Ankara (MVA) has been engineered to deliver the tumor antigen 5T4 ( TroVax). MVA-5T4 has been evaluated in an open-label phase 2 trial in metastatic renal cell cancer patients in which the vaccine was administered alone or in combination with interferon-alpha-2b (IFN-alpha). The safety, immunologic, and clinical efficacy of MVA-5T4 with or without IFN-alpha was determined. Twenty-eight patients with metastatic renal cell cancer were treated with MVA-5T4 alone (13) or plus IFN-alpha (15). The 5T4-specific cellular and humoral responses were monitored throughout the study. Clinical responses were assessed by measuring changes in tumor burden by computed tomography or magnetic resonance imaging scan. MVA-5T4 was well tolerated with no serious adverse event attributed to vaccination. Of 23 intent-to-treat patients tested for immune responses postvaccination, 22 (96%) mounted 5T4-specific antibody and/or cellular responses. One patient treated with MVA-5T4 plus IFN-alpha showed a partial response for >7 months, whereas an additional 14 patients (7 receiving MVA-5T4 plus IFN and 7 receiving MVA-5T4 alone) showed periods of disease stabilization ranging from 1.73 to 9.60 months. Median progression free survival and overall survival for all intent-to-treat patients was 3.8 months (range: 1 to 11.47 mo) and 12.1 months (range: 1 to 27 mo), respectively. MVA-5T4 administered alone or in combination with IFN-alpha was well tolerated in all patients. Despite the high frequency of 5T4-specific immune responses, it is not possible to conclude that patients are receiving clinical benefit. The results are encouraging and warrant further investigation.
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Authors | Robert J Amato, William Shingler, Madusha Goonewardena, Jackie de Belin, Stuart Naylor, Jaroslaw Jac, James Willis, Somyata Saxena, Joan Hernandez-McClain, Richard Harrop |
Journal | Journal of immunotherapy (Hagerstown, Md. : 1997)
(J Immunother)
Vol. 32
Issue 7
Pg. 765-72
(Sep 2009)
ISSN: 1537-4513 [Electronic] United States |
PMID | 19561532
(Publication Type: Clinical Trial, Phase II, Journal Article)
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Chemical References |
- Antibodies, Viral
- Cancer Vaccines
- Interferon-alpha
- TroVax
- Vaccines, DNA
- Interferon-gamma
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Topics |
- Adult
- Aged
- Anemia
(chemically induced)
- Antibodies, Viral
(blood)
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, immunology, therapeutic use)
- Cancer Vaccines
(administration & dosage, genetics, immunology)
- Carcinoma, Renal Cell
(drug therapy, immunology, pathology)
- Drug Delivery Systems
(methods)
- Enzyme-Linked Immunosorbent Assay
- Fatigue
(chemically induced)
- Female
- Fever
(chemically induced)
- Humans
- Interferon-alpha
(administration & dosage)
- Interferon-gamma
(immunology)
- Kidney Neoplasms
(drug therapy, immunology, pathology)
- Lymphopenia
(chemically induced)
- Male
- Middle Aged
- Survival Analysis
- Treatment Outcome
- Vaccination
(adverse effects, methods)
- Vaccines, DNA
- Vaccinia virus
(genetics, immunology)
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