A new peptide vaccine OCV-501: in vitro pharmacology and phase 1 study in patients with acute myeloid leukemia

Kobayashi, Yasuhito; Sakura, Toru; Miyawaki, Shuichi; Toga, Kouhei; Sogo, Shinji; Heike, Yuji

doi:10.1007/s00262-017-1981-3

Cited by 18 publications

(17 citation statements)

References 43 publications

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“…Furthermore, direct recognition and lysis of leukemia cells by WT1-specific CD4 + T lymphocytes were also reported [38]. Very recently, a phase I study of the OCV-501 peptide vaccine (WT1-332 helper peptide) for AML patients in CR showed that the s.c. vaccination was safe and well tolerated [39]. Here, a reduction in WT1 mRNA levels after the vaccination was observed in several patients.…”

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

confidence: 78%

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: Prospects For Enhancing the Efficacy And Usefulness Of The Wmentioning

confidence: 78%

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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“…In a recent phase I clinical study of the WT1 332 peptide vaccine (OCV-501), OCV-501 containing 0.3, 1.0, or 3.0 mg of the peptide was subcutaneously administered on a weekly basis to elderly patients with AML in complete remission for 4 weeks. This study demonstrated that OCV-501 was safe and well tolerated, and that WT1 332 peptide-specific delayed-type hypersensitivity occurred as an immunological response [27].…”

Section: Introductionmentioning

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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“…Analogous to CAR T cell therapy, antigen selection is crucial in development of cancer vaccine. Wilms' tumor protein 1 (WT1) is physiologically found at low levels in gonads, kidneys and normal hematopoietic tissue and is highly expressed in hematological malignancies including AML [97]. Yamaguchi et al evaluated the safety and efficacy of OCV-501, a synthetic peptide containing natural sequence of WT1, in a randomized, multicenter, double-blind, placebo-controlled trial [98].…”

Section: Vaccinesmentioning

confidence: 99%

Advances in Acute Myeloid Leukemia: Recently Approved Therapies and Drugs in Development

Stanchina

Soong

Zheng-Lin

et al. 2020

Cancers

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Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy comprised of various cytogenetic and molecular abnormalities that has notoriously been difficult to treat with an overall poor prognosis. For decades, treatment options were limited to either intensive chemotherapy with anthracycline and cytarabine-based regimens (7 + 3) or lower intensity regimens including hypomethylating agents or low dose cytarabine, followed by either allogeneic stem cell transplant or consolidation chemotherapy. Fortunately, with the influx of rapidly evolving molecular technologies and new genetic understanding, the treatment landscape for AML has dramatically changed. Advances in the formulation and delivery of 7 + 3 with liposomal cytarabine and daunorubicin (Vyxeos) have improved overall survival in secondary AML. Increased understanding of the genetic underpinnings of AML has led to targeting actionable mutations such as FLT3, IDH1/2 and TP53, and BCL2 or hedgehog pathways in more frail populations. Antibody drug conjugates have resurfaced in the AML landscape and there have been numerous advances utilizing immunotherapies including immune checkpoint inhibitors, antibody-drug conjugates, bispecific T cell engager antibodies, chimeric antigen receptor (CAR)-T therapy and the development of AML vaccines. While there are dozens of ongoing studies and new drugs in the pipeline, this paper serves as a review of the advances achieved in the treatment of AML in the last several years and the most promising future avenues of advancement

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A new peptide vaccine OCV-501: in vitro pharmacology and phase 1 study in patients with acute myeloid leukemia

Cited by 18 publications

References 43 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

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

Advances in Acute Myeloid Leukemia: Recently Approved Therapies and Drugs in Development

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