Dendritic cell vaccines for glioblastoma fail to complete clinical translation: Bottlenecks and potential countermeasures

Abstract

Glioblastoma (GBM) is a heterogeneous and invasive WHO grade IV brain tumor. Patients with GBM have a median overall survival (OS) of only 14 to 17 months when treated with surgical resection and chemoradiation. As one of the most promising anti-tumor immunotherapies, dendritic cell (DC) vaccines have demonstrated good efficacy, safety, and tolerability in many clinical trials. However, to date, no Phase III clinical trial has achieved positive endpoints and truly implement clinical development and transformation. Moreover, the survival benefits of DC vaccines for patients with GBM seem to have a delayed effect; therefore, we urgently require strategies to optimize DC vaccines to advance the time point of its survival benefits. Here, we discuss the latest clinical trial progress of DC vaccines in GBM and summarize the benefits and drawbacks of various vaccine design options, as well as the challenges faced in clinical translation. Moreover, we target future combination therapy strategies for DC vaccines in GBM, which provides a new perspective for comprehensively understanding the effectiveness, limitations, and new directions of the development of DC vaccines.

Keywords: Clinical translation; Combination therapy; Dendritic cell vaccine; Glioblastoma; Limitations.