Clinical effect and immunological response in patients with advanced malignant glioma treated with WT1-pulsed dendritic cell-based immunotherapy: A report of two cases

Abstract

Background: Dendritic cells (DCs), which are the most powerful antigen-presenting cells, activate innate and adaptive immune responses. Wilms' tumor 1 (WT1) is a tumor-associated antigen that is frequently expressed in many human cancers including gliomas and is therefore a potential target of immunotherapy for malignant gliomas. We report two cases with advanced malignant glioma that were treated in a clinical study of DC-based immunotherapy targeting WT1. Case description: In two patients with malignant glioma, the initial standard treatment failed, and the disease progressed. Subsequent WT1-pulsed DC vaccination resulted in a marked decrease in tumor size and an improvement in their performance status and neurological findings. The frequency of WT1-specific cytotoxic T lymphocytes increased after WT1-pulsed DC vaccination. No adverse events of grade 3 or worse were observed. The disease remained stable for 15 months in Case 1 and for 18 months in Case 2. However, both patients eventually died due to progressive disease. Conclusions: WT1-pulsed DC-based vaccination for two patients with advanced malignant glioma demonstrated the safety and immunogenicity. The present cases provide clinical evidence and an immunological response that DC vaccination induces tumor regression and improves neurological findings. Prospective clinical trials are required to evaluate the efficacy of acquired immunity in response to DC vaccination in improving the prognosis of advanced malignant glioma. Keywords: Dendritic cell, Wilms' tumor 1, Advanced malignant glioma, Immunotherapy