WT1 peptide vaccination following allogeneic stem cell transplantation in pediatric leukemic patients with high risk for relapse: successful maintenance of durable remission

Hashii, Yoshiko; Sato-Miyashita, E; Matsumura, Ryo; Kusuki, Shigenori; Yoshida, Hisao; Ohta, Hiroyuki; Hosen, Naoki; Tsuboi, Akihiro; Oji, Yusuke; Oka, Y.; Sugiyama, Haruo; Ozono, Keiichi

doi:10.1038/leu.2011.226

Cited by 51 publications

(41 citation statements)

References 15 publications

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“…Furthermore, in this group with higher-risk of relapse, WT1-associated cytotoxic T-lymphocyte therapy or vaccination may be used in near future. [35][36][37] Contrary to the expectations associated with the c-kit mutation, [12][13][14] our data showed a higher NRM rate rather than higher CIR rate after HSCT (Table 2). This might be caused by a higher proportion of allo-HSCT using myeloablative conditioning regimen producing higher therapy-related mortality, which was mainly conducted in c-kit-positive AML.…”

Section: Discussioncontrasting

confidence: 55%

Identification of molecular and cytogenetic risk factors for unfavorable core-binding factor-positive adult AML with post-remission treatment outcome analysis including transplantation

Kim

et al. 2014

Bone Marrow Transplant

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Emerging molecular studies have identified a subgroup of patients with unfavorable core-binding factor-positive (CBF)-AML who should be treated by intensified post-remission treatments. We analyzed 264 adults with CBF-AML from 2002 to 2011, and focused on 206 patients who achieved CR after standard '3+7' induction chemotherapy. Patients who achieved CR with an available donor were treated with allogeneic hematopoietic SCT (allo-HSCT, n = 115) and the rest were treated with autologous (auto) HSCT (n = 72) or chemotherapy alone (n = 19). OS was not significantly different between CBFβ/MYH11 (n = 62) and RUNX1/RUNX1T1 (n = 144), and auto-HSCT showed favorable OS compared with allo-HSCT or chemotherapy alone. Cytogenetic analysis identified that inv(16) without trisomy had a favorable OS and t(8;21) with additional chromosomes had an unfavorable OS, but multivariate analysis revealed those were NS. Patients with c-kit mutation showed inferior OS. For transplanted patients, residual post-transplant CBF-minimal residual disease quantitative PCR with higher WT1 expression at D+60 showed the worst OS with a higher incidence of relapse. Conclusively, we found that unfavorable CBF-AML can be defined with risk stratification using cytogenetic and molecular studies, and a careful risk-adapted treatment approach using frontline transplantation with novel therapies should be evaluated for this particular risk subgroup.

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Section: Discussioncontrasting

confidence: 55%

Identification of molecular and cytogenetic risk factors for unfavorable core-binding factor-positive adult AML with post-remission treatment outcome analysis including transplantation

Kim

et al. 2014

Bone Marrow Transplant

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“…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: 96%

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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“…A phase II clinical trial in AML and high-risk MDS using a WT1 peptide vaccine demonstrated that an immunologic response was observed in 44% patients, and objective clinical responses were observed in 10 out of 17 AML patients [18]. While there are reports from small case series which have suggested that WT1 vaccination can have long term efficacy in patients [19,20], other groups have observed that that repeated peptide vaccination in Montanide failed to induce sustained high-avidity, epitope-specific T cell responses in treated patients [21]. In addition, Lehe et al [22] generated WT1 specific T-cell clones which carried a CD4…”

Section: Wt1 Is a Leukemia Associated Antigenmentioning

confidence: 99%

Novel Immunotherapy to Eliminate Minimal Residual Disease in AML Patients

Liu

Kline²

2013

J Hematol Thrombo Diseases

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Even with the most sophisticated chemotherapy regimens, the majority of patients with acute myeloid leukemia will eventually experience a relapse and die from their disease. New treatments are needed to prevent relapse of disease in these patients. Immunotherapy using the host immune system to combat leukemia represents an exciting and potentially efficacious addition to standard chemotherapy for AML. Immune-base treatments may be particularly effective when administered at a time when patients are in clinical remission with normal blood counts; nevertheless, these patients often have minimal residual disease which eventually results in disease relapse. Successful vaccinationbased immunotherapy targeting leukemia-specific antigens will likely require the administration of powerful immune adjutants and removal of negative immune regulatory pathways in order to achieve maximal efficacy. This review article will focus on the rationales underlying our ongoing clinical trial to test the efficacy of WT1 peptide based immunotherapy using TLR3 agonist as adjuvant in combination of the depletion of T regulatory cells with anti-CD25 antibody in patients with hematologic malignancies.

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WT1 peptide vaccination following allogeneic stem cell transplantation in pediatric leukemic patients with high risk for relapse: successful maintenance of durable remission

Cited by 51 publications

References 15 publications

Identification of molecular and cytogenetic risk factors for unfavorable core-binding factor-positive adult AML with post-remission treatment outcome analysis including transplantation

Identification of molecular and cytogenetic risk factors for unfavorable core-binding factor-positive adult AML with post-remission treatment outcome analysis including transplantation

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

Novel Immunotherapy to Eliminate Minimal Residual Disease in AML Patients

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