Wilms tumour 1 peptide vaccine as a cure‐oriented post‐chemotherapy strategy for patients with acute myeloid leukaemia at high risk of relapse

Nakata, Jun; Nakae, Yoshiki; Kawakami, Manabu; Morimoto, Soyoko; Motooka, Daisuke; Hosen, Naoki; Fujiki, Fumihiro; Nakajima, Hiroyuki; Hasegawa, Kana; Nishida, Sumiyuki; Tsuboi, Akihiro; Oji, Yusuke; Oka, Y.; Kumanogoh, Atsushi; Sugiyama, Haruo

doi:10.1111/bjh.14768

Cited by 21 publications

(16 citation statements)

References 20 publications

(28 reference statements)

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“…Very recently, Nakata et al [32] also reported a favorable result with the WT1 peptide vaccine in the context of a cure-oriented strategy. HLA-A*0201 or HLA-A*2402-positive AML patients in CR but at high risk of relapse after chemotherapy, including those with MRD at the molecular level, were i.d.…”

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

confidence: 99%

“…Furthermore, it can currently be expected that, when patients with certain types of hematological malignancies in CR but at high risk of relapse are treated with the WT1 peptide vaccine, they can attain long-lasting relapse-free survival, which may lead to a cure, with minimal side effects [25,27,[30][31][32]35]. The results of studies performed so far have made it possible to make several proposals that may allow the WT1 peptide vaccine to exert its maximum beneficial action (table 1).…”

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

confidence: 99%

“…First, the vaccination of patients with MRD should be an important strategy for the vaccine to show its maximum effect [25,27,[30][31][32]35]. AML patients in CR but at high risk of relapse after chemotherapy are good candidates for this situation [31,32,35].…”

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

confidence: 99%

“…AML patients in CR but at high risk of relapse after chemotherapy are good candidates for this situation [31,32,35]. 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].…”

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

confidence: 99%

“…Not only clinical but also basic research-related data, such as those about clonality or gene expression profiles of WT1-specific CTLs, have been accumulated with the analysis of blood samples obtained from previous clinical studies [32,43,44], that is, reverse translational research. Blood samples obtained from ongoing and future clinical studies, including those proposed here, should further contribute to accumulating valuable findings about cancer immunology at the cellular and molecular level.…”

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 Phamentioning

confidence: 99%

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

confidence: 99%

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

confidence: 99%

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

confidence: 99%

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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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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Identification of mouse helper epitopes for WT1-specific CD4+ T cells

Nakajima

Nakata

Imafuku

et al. 2021

Cancer Immunol Immunother

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Wilms tumour 1 peptide vaccine as a cure‐oriented post‐chemotherapy strategy for patients with acute myeloid leukaemia at high risk of relapse

Cited by 21 publications

References 20 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

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

Identification of mouse helper epitopes for WT1-specific CD4+ T cells

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Wilms tumour 1 peptide vaccine as a cure‐oriented post‐chemotherapy strategy for patients with acute myeloid leukaemia at high risk of relapse

Cited by 21 publications

References 20 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

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

Identification of mouse helper epitopes for WT1-specific CD4+ 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