title: Active specific immunotherapy targeting the Wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: lessons from early clinical trials.
abstract: There is a growing body of evidence that Wilms' tumor protein 1 (WT1) is a promising tumor antigen for the development of a novel class of universal cancer vaccines. Recently, in a National Cancer Institute prioritization project, WT1 was ranked first in a list of 75 cancer antigens. In this light, we exhaustively reviewed all published cancer vaccine trials reporting on WT1-targeted active specific immunotherapy in patients with hematological malignancies and solid tumors. In all clinical trials, vaccine-induced immunological responses could be detected. Importantly, objective clinical responses (including stable disease) were observed in 46% and 64% of evaluable vaccinated patients with solid tumors and hematological malignancies, respectively. Immunogenicity of WT1-based cancer vaccines was demonstrated by the detection of a specific immunological response in 35% and 68% of evaluable patients with solid tumors and hematological malignancies, respectively. In order to become part of the armamentarium of the modern oncologist, it will be important to design WT1-based immunotherapies applicable to a large patient population, to standardize vaccination protocols enabling systematic review, and to further optimize the immunostimulatory capacity of the vaccine components. Moreover, improved immunomonitoring tools that reveal clinically relevant T-cell responses will further shape the ideal WT1 immunotherapy strategy. In conclusion, the clinical results obtained so far in WT1-targeted cancer vaccine trials reveal an untapped potential for inducing cancer immunity with minimal side effects and hold promise for a new adjuvant treatment against residual disease and against cancer relapse.
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VaxInfectio), Faculty of Medicine, University of Antwerp, Antwerp, Belgium. ann.van.driessche@uza.be
authors.forename: Ann
authors.initials: A
authors.lastname: Van Driessche
authors.forename: Zwi N
authors.initials: ZN
authors.lastname: Berneman
authors.forename: Viggo F I
authors.initials: VF
authors.lastname: Van Tendeloo
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology*; D002986:Clinical Trials as Topic; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D016233:Immunotherapy, Active / Q000009:adverse effects; D009369:Neoplasms / Q000628:therapy*; D025721:WT1 Proteins / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D025721:WT1 Proteins