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

Nirali N. Shah, David M. Loeb, Hahn Khuu, David Stroncek, Tolu Ariyo, Mark Raffeld, Cindy Delbrook, Crystal L. Mackall, Alan S. Wayne, Terry J. Fry

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2149-2154
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number12
DOIs
StatePublished - Dec 1 2016

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Wilms Tumor
Hematologic Neoplasms
Dendritic Cells
Hematopoietic Stem Cell Transplantation
Vaccination
Transplantation
Tissue Donors
Lymphocytes
Recurrence
Leukemia
Vaccines
Delayed Hypersensitivity
Graft vs Host Disease
Wilms' Tumor Genes
Active Immunotherapy
Skin
Cancer Vaccines
Neoplasm Antigens
Pruritus
Secondary Prevention

Keywords

  • Dendritic cell vaccine
  • Leukemia
  • Post-transplantation relapse
  • Wilms' tumor 1 (WT1)

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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. / Shah, Nirali N.; Loeb, David M.; Khuu, Hahn; Stroncek, David; Ariyo, Tolu; Raffeld, Mark; Delbrook, Cindy; Mackall, Crystal L.; Wayne, Alan S.; Fry, Terry J.

In: Biology of Blood and Marrow Transplantation, Vol. 22, No. 12, 01.12.2016, p. 2149-2154.

Research output: Contribution to journalArticle

Shah, Nirali N. ; Loeb, David M. ; Khuu, Hahn ; Stroncek, David ; Ariyo, Tolu ; Raffeld, Mark ; Delbrook, Cindy ; Mackall, Crystal L. ; Wayne, Alan S. ; Fry, Terry J. / 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. In: Biology of Blood and Marrow Transplantation. 2016 ; Vol. 22, No. 12. pp. 2149-2154.
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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.",
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