title: Induction of Immune Response after Allogeneic Wilms' Tumor 1 Dendritic Cell Vaccination and Donor Lymphocyte Infusion in Patients with Hematologic Malignancies and Post-Transplantation Relapse.
abstract: Relapse of hematologic malignancies is the primary cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HCT). Treatment for post-HCT relapse using donor lymphocyte infusion (DLI) has limited utility, particularly in the setting of acute leukemia, and can result in the development of graft-versus-host disease (GVHD). The Wilms' tumor 1 (WT1) gene product is a tumor-associated antigen that is expressed in acute leukemia and other hematologic malignancies, with limited expression in normal tissues. In this pilot trial, we assessed safety and feasibility of a WT1 peptide-loaded donor-derived dendritic cell (DC) vaccine given with DLI designed to enhance and direct the graft-versus-leukemia effect. Secondary objectives were to evaluate immunologic and clinical responses. A total of 5 subjects, median age 17 years (range, 9 to 19 years), with post-HCT relapse were enrolled. Disease subtypes included acute lymphoblastic leukemia (n = 3), acute myelogenous leukemia (n = 1), and Hodgkin lymphoma (n = 1). Successful vaccine production was feasible from all donors. DC vaccination and DLI were well tolerated. One recipient developed grade 1 skin GVHD not requiring systemic therapy. The most common adverse events included grade 1 reversible pain and pruritus at the vaccine injection and delayed-type hypersensitivity (DTH) skin testing sites. There were no grade 3 or higher adverse events related to the research. Immune responses consisted of ELISpot response in 3 recipients and positive DTH tests to WT1 peptide cocktail in 2 subjects. Our study provides 1 of the first attempts to apply tumor-specific vaccine therapy to the allogeneic setting. Preliminary results show the DC-based vaccination is safe and feasible after allogeneic HCT, with a suggestion that this approach can be used to sensitize the repopulated allogeneic-donor immune system to WT1. Future directions may include testing of vaccination strategies in the early post-transplantation setting for relapse prevention.
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: Nirali.Shah@nih.gov.
authors.forename: Nirali N
authors.initials: NN
authors.lastname: Shah
authors.affiliation: Pediatric Oncology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: David M
authors.initials: DM
authors.lastname: Loeb
authors.affiliation: Department of Transfusion Medicine, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Hahn
authors.initials: H
authors.lastname: Khuu
authors.affiliation: Department of Transfusion Medicine, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Stroncek
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Tolu
authors.initials: T
authors.lastname: Ariyo
authors.affiliation: Univerity of Southern California-Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Cindy
authors.initials: C
authors.lastname: Delbrook
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Mackall
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, Los Angeles, California.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Wayne
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Fry
mesh_terms: D000293:Adolescent; D000328:Adult; D019496:Cancer Vaccines / Q000276:immunology*; D002648:Child; D003713:Dendritic Cells / Q000737:chemistry / Q000637:transplantation*; D006086:Graft vs Host Disease / Q000473:pathology; D020544:Graft vs Leukemia Effect; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D017710:Lymphocyte Transfusion; D012008:Recurrence; D025721:WT1 Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines; D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: Dendritic cell vaccine; Leukemia; Post-transplantation relapse; Wilms' tumor 1 (WT1)