Elsevier

Cytotherapy

Volume 17, Issue 3, March 2015, Pages 330-335
Cytotherapy

Original paper
Cancer therapy
Safety and tolerability of allogeneic dendritic cell vaccination with induction of Wilms tumor 1–specific T cells in a pediatric donor and pediatric patient with relapsed leukemia: a case report and review of the literature

https://doi.org/10.1016/j.jcyt.2014.10.003Get rights and content

Abstract

A 15-year-old girl with acute lymphoblastic leukemia received allogeneic dendritic cell vaccination, pulsed with Wilms tumor 1 (WT1) peptide, after her third hematopoietic stem cell transplantation (HSCT). The vaccines were generated from the third HSCT donor, who was her younger sister, age 12 years. The patient received 14 vaccines and had no graft-versus-host disease or systemic adverse effect, aside from grade 2 skin reaction at the injection site. WT1-specific immune responses were detected after vaccination by both WT1-tetramer analysis and enzyme-linked immunosorbent spot assay. This strategy may be safe, tolerable and even feasible for patients with a relapse after HSCT.

Introduction

The outcome of patients with relapsed leukemia after allogeneic hematopoietic stem cell transplantation (HSCT) is discouraging and indicates an urgent need for new therapies [1]. Donor lymphocyte infusion (DLI) has been proposed to overcome leukemic relapse after HSCT by boosting graft-versus-leukemia effect. However, DLI provokes unmanageable graft-versus-host disease (GVHD) because many allogeneic antigens are targeted by donor T cells [2].

Leukemic antigen-specific autologous dendritic cell (DC)-based vaccination for hematological malignancies is currently explored to avoid off-target effects [3], [4]. The autologous DC therapy requires the production of DC vaccines from patient-derived peripheral blood mononuclear cells (PBMCs) through the use of leukapheresis. Although healthy donor-derived PBMCs may be available to generate the allogeneic DC vaccines in the patients who received HSCT, little has been reported on the safety and tolerability of the production and administration of donor-derived DCs for the donor and recipient. Additionally, the induction of leukemic antigen-specific T cells by allogeneic DC vaccines remains unclear.

Thus, we conducted a phase I clinical trial to test the safety and tolerability of Wilms tumor 1 (WT1)-specific allogeneic DC vaccination for pediatric patients with relapsed leukemia after HSCT. We report the results from the first patient who completed the allogeneic DC vaccination.

Section snippets

Patients

This clinical trial (UMIN: 000002105) was approved by the institutional review board of the Shinshu University School of Medicine. Written informed consent was obtained from patients over 12 years of age, HSCT donors and their parents, according to the Helsinki Declaration. Adverse effects were graded by use of the National Cancer Institute's Common Toxicity Criteria version 3.

Preparation of allogeneic DC vaccine

Mature DCs (mDCs) were generated under Good Manufacturing Practice conditions and cryopreserved in liquid nitrogen as

Transplantations and lymphocyte infusions

A 12-year-old girl was diagnosed with B-precursor acute lymphoblastic leukemia. She underwent allogeneic bone marrow transplantation from her mother (HLA 8/8 allele-match) in first complete remission (CR) (first HSCT, Figure 1). The engraftment was successful, but she had a hematological relapse 11 months after this first HSCT. A combination of chemotherapy and two sessions of donor lymphocyte infusion (DLI) did not induce long-term remission. Consequently, she was transplanted with peripheral

Discussion

This study describes the treatment of the youngest donor and recipient for allogeneic DC vaccination. We successfully generated 15 doses of DC vaccine (1 × 107 cells/dose) safely from a 12-year-old, healthy donor, with a single leukapheresis session. The 14 doses of allogeneic DC vaccination pulsed with WT1235–243 peptide were all safe and well tolerated by the 15-year-old patient, without adverse effects except for a grade 2 local reaction. A literature review identified six patients with

Acknowledgments

We wish to thank nurse Kayo Horiuchi for taking care of the patients and harvesting the PBMCs from the HSCT donor. This clinical trial was supported by Management Expense Grants from the Ministry of Education, Culture, Sports, Science and Technology, Japan (grant number: 24501330 and 24791050).

Disclosure of interests: The authors have no commercial, proprietary, or financial interest in the products or companies described in this article.

References (13)

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