title: Vaccination of renal cell cancer patients with modified vaccinia Ankara delivering the tumor antigen 5T4 (TroVax) alone or administered in combination with interferon-alpha (IFN-alpha): a phase 2 trial.
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.
authors: Memorial Hermann Cancer Center, The University of Texas Health Science Center, Houston, TX 77030, USA.
authors: Robert J
authors: RJ
authors: Amato
authors: William
authors: W
authors: Shingler
authors: Madusha
authors: M
authors: Goonewardena
authors: Jackie
authors: J
authors: de Belin
authors: Stuart
authors: S
authors: Naylor
authors: Jaroslaw
authors: J
authors: Jac
authors: James
authors: J
authors: Willis
authors: Somyata
authors: S
authors: Saxena
authors: Joan
authors: J
authors: Hernandez-McClain
authors: Richard
authors: R
authors: Harrop
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000914:Antibodies, Viral / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016503:Drug Delivery Systems / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007371:Interferon-gamma / Q000276:immunology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome; D014611:Vaccination / Q000009:adverse effects / Q000379:methods; D019444:Vaccines, DNA; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019496:Cancer Vaccines; D016898:Interferon-alpha; C504058:TroVax; D019444:Vaccines, DNA; D007371:Interferon-gamma