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

Oka, Y.; Tsuboi, Akihiro; Nakata, Jun; Nishida, Sumiyuki; Hosen, Naoki; Kumanogoh, Atsushi; Oji, Yusuke; Sugiyama, Haruo

doi:10.1159/000481353

Cited by 34 publications

(31 citation statements)

References 44 publications

(79 reference statements)

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“…We previously treated hematopoietic malignancies including leukemia and various kinds of solid tumors with WT1 HLA class I peptide vaccine and reported that the vaccination elicited WT1-specific immunological response, followed by clinical responses without severe adverse effects [29]. One of the most important problems of WT1 vaccination with WT1 HLA class I peptide alone was that WT1-specific CD8 + T cells generally increased at 4–8 weeks post-WT1 vaccination, but afterwards decreased gradually, and their frequency could not be maintained for a long time (data not shown).…”

Section: Discussionmentioning

confidence: 99%

A phase I clinical study of a cocktail vaccine of Wilms’ tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma

Tsuboi

Hashimoto

Fujiki

et al. 2018

Cancer Immunol Immunother

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Purpose The safety and clinical efficacy of WT1 human leukocyte antigen (HLA) class I peptide vaccine have been established, but the safety of a cocktail vaccine of WT1 HLA class I and II peptides has not. To verify its safety, we performed a phase I clinical trial for patients with recurrent malignant gliomas and assessed the immunological responses and survival data. Patients and methods Fourteen HLA-A*24:02-positive patients with recurrent malignant glioma (2 with grade 3, 12 with grade 4) were enrolled. Every week, the patients received alternately a vaccine containing 3 mg of WT1 HLA-A*24:02-restricted (HLA class I) peptide and a cocktail vaccine of the HLA class I peptide and one of 0.75, 1.5 or 3 mg of the WT1 HLA class II peptide. For patients who showed no significant adverse effects within 6 weeks, the WT1 vaccine was continued at 2–4-week intervals. Results Eleven of the 14 patients completed WT1 vaccination for 6 weeks, while 3 patients dropped out earlier due to disease progression. All patients showed grade I level of skin disorders at the injection sites. No grade III/IV toxicity or dose-limiting toxicity was observed for any dose of WT1 HLA class II peptide. Six of the 14 patients had stable disease at 6 weeks. Median OS and 1-year OS rates were 24.7 weeks and 36%, respectively. Conclusion The safety of a cocktail vaccine of WT1 HLA class I and II peptides for malignant gliomas was verified. This vaccine is, therefore, considered promising for patients with recurrent malignant glioma.

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Section: Discussionmentioning

confidence: 99%

A phase I clinical study of a cocktail vaccine of Wilms’ tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma

Tsuboi

Hashimoto

Fujiki

et al. 2018

Cancer Immunol Immunother

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“…Interestingly, WT1 was ranked as the top immunotherapy target in cancer by a national cancer institute pilot project for the prioritization of cancer antigens [117]. Numerous clinical studies were carried out implementing peptide vaccination strategies for AML patients in remission after an initial chemotherapy and demonstrated that they are able to induce T-cell responses and are well tolerated with only minor side effects [79,118,119,120]. Furthermore, DC vaccination and adoptive transfer of WT1-specific cytotoxic T cells showed to be auspicious therapeutic options in combination with allogeneic stem cell transplantation in AML patients [121,122].…”

Section: Hla-dependent Antigensmentioning

confidence: 99%

Antigen Targets for the Development of Immunotherapies in Leukemia

Bauer

Nelde

Bilich

et al. 2019

IJMS

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Immunotherapeutic approaches, including allogeneic stem cell transplantation and donor lymphocyte infusion, have significantly improved the prognosis of leukemia patients. Further efforts are now focusing on the development of immunotherapies that are able to target leukemic cells more specifically, comprising monoclonal antibodies, chimeric antigen receptor (CAR) T cells, and dendritic cell- or peptide-based vaccination strategies. One main prerequisite for such antigen-specific approaches is the selection of suitable target structures on leukemic cells. In general, the targets for anti-cancer immunotherapies can be divided into two groups: (1) T-cell epitopes relying on the presentation of peptides via human leukocyte antigen (HLA) molecules and (2) surface structures, which are HLA-independently expressed on cancer cells. This review discusses the most promising tumor antigens as well as the underlying discovery and selection strategies for the development of anti-leukemia immunotherapies.

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“…Moreover, WT1 has been ranked at the top position in the National Cancer Institute's (NCI) list of cancer antigens with the highest prioritization for vaccine development (221). The use of peptide vaccines against the WT1 antigen showed beneficial therapeutic outcomes in several clinical trials (222, 223).…”

Section: Classification Of Mbpsmentioning

confidence: 99%

DNA Methylation Readers and Cancer: Mechanistic and Therapeutic Applications

2019

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DNA methylation is a major epigenetic process that regulates chromatin structure which causes transcriptional activation or repression of genes in a context-dependent manner. In general, DNA methylation takes place when methyl groups are added to the appropriate bases on the genome by the action of “writer” molecules known as DNA methyltransferases. How these methylation marks are read and interpreted into different functionalities represents one of the main mechanisms through which the genes are switched “ON” or “OFF” and typically involves different types of “reader” proteins that can recognize and bind to the methylated regions. A tightly balanced regulation exists between the “writers” and “readers” in order to mediate normal cellular functions. However, alterations in normal methylation pattern is a typical hallmark of cancer which alters the way methylation marks are written, read and interpreted in different disease states. This unique characteristic of DNA methylation “readers” has identified them as attractive therapeutic targets. In this review, we describe the current state of knowledge on the different classes of DNA methylation “readers” identified thus far along with their normal biological functions, describe how they are dysregulated in cancer, and discuss the various anti-cancer therapies that are currently being developed and evaluated for targeting these proteins.

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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

Cited by 34 publications

References 44 publications

A phase I clinical study of a cocktail vaccine of Wilms’ tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma

A phase I clinical study of a cocktail vaccine of Wilms’ tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma

Antigen Targets for the Development of Immunotherapies in Leukemia

DNA Methylation Readers and Cancer: Mechanistic and Therapeutic Applications

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