Feasibility of Cancer Immunotherapy with WT1 Peptide Vaccination for Solid and Hematological Malignancies in Children

Sawada, Akihisa; Inoue, Masami; Kondo, Osamu; Yamada-Nakata, Kayo; Ishihara, Takashi; Kuwae, Yuko; Nishikawa, Masanori; Ammori, Yasuhiro; Tsuboi, Akihiro; Oji, Yusuke; Koyama-Sato, Maho; Oka, Y.; Yasui, Masayoshi; Sugiyama, Haruo; Kawa, Keisei

doi:10.1002/pbc.25792

Cited by 27 publications

(18 citation statements)

References 23 publications

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“…Since allo-HSCT is a kind of immunotherapy targeting alloantigens, the WT1 peptide vaccination after allo-HSCT constitutes a combination treatment comprising 2 different immunotherapies. Consistent with this result, Sawada et al [26] also reported that a pediatric patient with ALL, who was in CR but at high risk of relapse after allo-HSCT and was treated with the vaccine, showed long-lasting CR. In 2013, Maeda et al [27] reported promising results for the WT1 peptide vaccination after allo-HSCT for the prevention of relapse of AML and ALL, in which HLA-A*2402-positive adult patients were treated by i.d.…”

Section: Clinical Studies Of Wt1 Peptide Vaccine In the 'Advanced Phasupporting

confidence: 67%

“…As is described later in more detail, patients with acute lymphoblastic leukemia (ALL) in CR but with a high risk of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) showed long-term maintenance of CR when treated with the WT1 peptide vaccine, which strongly suggests that ALL also constitutes a target disease for this vaccine therapy [25][26][27].…”

Section: Potential Target Hematological Malignancies Other Than Aml Amentioning

confidence: 97%

“…Patients with aggressive hematological malignancies such as acute leukemia who have received allo-HSCT but still have MRD are also good candidates for use of the vaccine to its maximum effect [25,27,35]. Of note, patients with ALL, as well as those with AML, who underwent WT1 peptide vaccine therapy in CR after allo-HSCT showed long-term survival [25][26][27], which suggests that ALL cells are also sensitive to WT1 peptide vaccination.…”

Section: Prospects For Enhancing the Efficacy And Usefulness Of The Wmentioning

confidence: 99%

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Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy

et al. 2017

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The identification of human Wilms' tumor gene 1 (WT1) protein-derived cytotoxic T lymphocyte (CTL) epitopes and the in vivo efficacy of WT1 peptide-based immunotherapy in a mouse model were reported in 2000. This successful basic research led to clinical studies of a WT1 peptide vaccine, and a positive impact on clinical response was first demonstrated in 2003 in the form of a reduction in blast cells of vaccine-treated patients with myelodysplastic syndromes (MDS). Since then, data on WT1 peptide vaccine-treated patients with immunological and/or clinical response have been accumulated. MDS and acute myeloid leukemia were the major target diseases to provide proof of concept for the therapeutic potential of the WT1 peptide vaccine. WT1 vaccination-induced clinical responses or usefulness were also shown for chronic myeloid leukemia, multiple myeloma, and acute lymphoblastic leukemia, as well as various types of solid cancers. Non-Hodgkin's lymphoma and myeloproliferative neoplasms may also be target diseases because of their WT1 expression. Of note, recent clinical studies have demonstrated that patients with hematological malignancies who have minimal residual disease after chemotherapy or allogeneic hematopoietic stem cell transplantation may be cured by WT1 peptide vaccination. Further enhancement of the efficacy and usefulness of the WT1 peptide vaccine is expected.

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Section: Clinical Studies Of Wt1 Peptide Vaccine In the 'Advanced Phasupporting

confidence: 67%

Section: Potential Target Hematological Malignancies Other Than Aml Amentioning

confidence: 97%

Section: Prospects For Enhancing the Efficacy And Usefulness Of The Wmentioning

confidence: 99%

See 1 more Smart Citation

Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy

et al. 2017

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“…[16][17][18][19] In this pilot study, despite the small number of patients, we describe one of the first attempts to apply DC-based cancer vaccines to the allogeneic setting. We demonstrate that not only is this approach safe and feasible, but that vaccination can be used to sensitize the allogeneic donor Although the allogeneic effect contributes to the success of HCT in ALL, a number of factors are believed to limit the GVL effect in ALL, making the immune response seen in this trial even more notable.…”

Section: Discussionmentioning

confidence: 98%

“…Experience with DC vaccination, particularly in the allogeneic post-transplant setting, is limited. [16][17][18][19] We describe results from a pilot trial that incorporates antigen-specific immunotherapy and allogeneic adoptive cell transfer for pediatric and adult patients with relapsed hematologic malignancies after allogeneic HCT using GMP methods for ex vivo generation of monocytederived dendritic cells. 20 The primary objectives were to assess safety and feasibility of a WT1 peptide-loaded, HLA-A2 restricted, allogeneic donor-derived dendritic cell (DC) vaccine designed to enhance the GVL effect of co-administered DLI.…”

Section: Introductionmentioning

confidence: 99%

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

Loeb

Khuu

et al. 2016

Biology of Blood and Marrow Transplantation

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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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Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141⁺ dendritic cells to activate naïve and memory WT1‐specific CD8⁺ T cells

et al. 2020

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ObjectivesVaccines that prime Wilms' tumor 1 (WT1)‐specific CD8+ T cells are attractive cancer immunotherapies. However, immunogenicity and clinical response rates may be enhanced by delivering WT1 to CD141+ dendritic cells (DCs). The C‐type lectin‐like receptor CLEC9A is expressed exclusively by CD141+ DCs and regulates CD8+ T‐cell responses. We developed a new vaccine comprising a human anti‐CLEC9A antibody fused to WT1 and investigated its capacity to target human CD141+ DCs and activate naïve and memory WT1‐specific CD8+ T cells.MethodsWT1 was genetically fused to antibodies specific for human CLEC9A, DEC‐205 or β‐galactosidase (untargeted control). Activation of WT1‐specific CD8+ T‐cell lines following cross‐presentation by CD141+ DCs was quantified by IFNγ ELISPOT. Humanised mice reconstituted with human immune cell subsets, including a repertoire of naïve WT1‐specific CD8+ T cells, were used to investigate naïve WT1‐specific CD8+ T‐cell priming.ResultsThe CLEC9A‐WT1 vaccine promoted cross‐presentation of WT1 epitopes to CD8+ T cells and mediated priming of naïve CD8+ T cells more effectively than the DEC‐205‐WT1 and untargeted control‐WT1 vaccines.ConclusionsDelivery of WT1 to CD141+ DCs via CLEC9A stimulates CD8+ T cells more potently than either untargeted delivery or widespread delivery to all Ag‐presenting cells via DEC‐205, suggesting that cross‐presentation by CD141+ DCs is sufficient for effective CD8+ T‐cell priming in humans. The CLEC9A‐WT1 vaccine is a promising candidate immunotherapy for malignancies that express WT1.

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Feasibility of Cancer Immunotherapy with WT1 Peptide Vaccination for Solid and Hematological Malignancies in Children

Cited by 27 publications

References 23 publications

Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy

Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy

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

Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141⁺ dendritic cells to activate naïve and memory WT1‐specific CD8⁺ T cells

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Feasibility of Cancer Immunotherapy with WT1 Peptide Vaccination for Solid and Hematological Malignancies in Children

Cited by 27 publications

References 23 publications

Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy

Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy

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

Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1‐specific CD8+ T cells

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Product

Resources

About

Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141⁺ dendritic cells to activate naïve and memory WT1‐specific CD8⁺ T cells