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

Yukio Kobayashi,Shinji Sogo,Yuji Heike,Toru Sakura,Shuichi Miyawaki,Kazuyuki Toga

doi:10.1007/s00262-017-1981-3

Abstract

Wilms’ tumor 1 (WT1) is a promising target of new immunotherapies for acute myeloid leukemia (AML) as well as for other cancers. OCV-501 is a helper peptide derived from the WT1 protein. OCV-501 induced OCV-501-specific Type 1 T-helper (Th1) responses dose-dependently and stimulated helper activity of the specific Th1 cells in peripheral blood mononuclear cells from healthy donors. OCV-501 also enhanced the increase in WT1-killer peptide-specific cytotoxic T lymphocytes. OCV-501 stimulated the OCV-501-specific Th1 clones in an HLA class-II restricted manner and formed a complex with HLA class-II protein. OCV-501-specific Th1 clones demonstrated significant OCV-501-specific cytolytic activity against OCV-501-pulsed B-lymphoblastoid cell line cells. Based on the pre-clinical results, phase 1 clinical trial was conducted. The result of this trial suggested that the subcutaneous administration of OCV-501 once weekly for 4 weeks at doses of 0.3, 1, and 3 mg in older patients with AML during complete remission was safe and well tolerated. The maximum tolerated dose was considered to be ≥3 mg. Of the nine subjects enrolled, neither relapse nor blast cells were observed during the study. Immunological responses were observed in OCV-501-specific delayed-type hypersensitivity test. This trial was registered at http://www.clinicaltrials.gov as NCT 01440920.

Highlights

Acute myeloid leukemia (AML) is the most common leukemia in older adults
From day 7 to day 14, OCV-501-specific Th1 cells were significantly expanded in OCV-501 culture using human peripheral blood mononuclear cells (PBMC) of 20 healthy donors as shown in Fig. 1a, but not in solvent culture (p = 0.0005)
OCV-501 enhanced the increase in Wilms’ tumor 1 (WT1)-126-specific CTLs in 3 out of 3 samples (Fig. 1d) and WT1-235mu-specific CTLs in 6 of 8 samples (Fig. 1e) in the presence of PBMC-derived OCV501-specific Th1 cells and WT1-killer peptide (WT1-126 or WT1-235mu)-specific CTLs

Summary

Introduction

Acute myeloid leukemia (AML) is the most common leukemia in older adults. Chemotherapy is a standard treatment for patients with AML and is usually divided into remission induction and consolidation therapy. Complete remission (CR) rates in younger patients exceeded 70%, but declined to 50% in older patients [1]. One of the major obstacles to curing AML, in older patients, is its propensity to relapse after the achievement of CR with chemotherapy or hematopoietic stem-cell transplantation [2]. New therapeutic strategies for preventing relapse after consolidation therapy for AML are urgently needed. The graft versus leukemia effect associated with allogeneic hematopoietic stem cell transplantation strongly suggests that immunotherapy is a promising AML treatment [3, 4]. Recent studies have identified several promising AML antigens as targets of immunotherapy [4]. Wilms’ tumor 1 (WT1) antigen is acknowledged as a top-ranked among 75 cancer antigens [5]

Methods

Results

Conclusion