Active dendritic cell immunotherapy for glioblastoma: Current status and challenges

Abstract

Dendritic cell (DC) immunotherapy is developing as a promising treatment modality for patients with glioblastoma multiforme (GBM). The aim of this article is to review the data from clinical trials and prospective studies evaluating the safety and efficacy of DC vaccines for newly diagnosed (ND)- and recurrent (Rec)-GBM and for other high-grade gliomas (HGGs). By searching all major databases we identified and reviewed twenty-two (n=22) such studies, twenty (n=20) of which were phase I and II trials, one was a pilot study towards a phase I/II trial and one was a prospective study. GBM patients were exclusively recruited in 12/22 studies, while 10/22 studies enrolled patients with any diagnosis of a HGG. In 7/22 studies GBM was newly diagnosed. In the vast majority of studies the vaccine was injected subcutaneously or intradermally and consisted of mature DCs pulsed with tumour lysate or peptides. Median overall survival ranged between 16.0 and 38.4 months for ND-GBM and between 9.6 and 35.9 months for Rec-GBM. Vaccine-related side effects were in general mild (grade I and II), with serious adverse events (grade III, IV and V) reported only rarely. DC immunotherapy therefore appears to have the potential to increase the overall survival in patients with HGG, with an acceptable side effect profile. The findings will require confirmation by the ongoing and future phase III trials.

Preclinical efficacy of immune-checkpoint monotherapy does not recapitulate corresponding biomarkers-based clinical predictions in glioblastoma

“…2 However, even this only marginally improves the prognosis of GBM patients. [3][4][5] This disturbingly negative situation advocates application of novel anti-GBM therapies.…”

“…1,2 GBM is resistant to most existing multimodal therapies. [3][4][5] Nearly 160 FDA-approved anti-GBM drugs have been applied, yet only a few are implemented as standard-of-care (e.g., temozolomide, since 2005). 2 Current GBM treatment paradigm consists of maximal surgical resection followed by radiotherapy plus temozolomide.…”

Strategies to Improve Vaccine Efficacy against Tuberculosis by Targeting Innate Immunity

“…Apoptotic tumor cells increased the survival rates of mice. These data suggest that antigens delivered by apoptotic cells to antigen-presenting cells can result in a stronger T cell response than those carried by necrotic cells ( 42 ). This notion is corroborated by a study, which combined dendritic cell-based immunotherapy with immunogenic cell death to successfully elicit Th1-mediated immunity to glioma ( 43 ).…”

Integrating Next-Generation Dendritic Cell Vaccines into the Current Cancer Immunotherapy Landscape

“…Moreover, if we compare the overall clinical-ORRs landscape for melanoma, GBM and RCC, an interesting picture emerges ( Figure 4b). For decades, the ORRs achieved by chemotherapy (mainly dacarbazine) or radio-/chemo-therapy (mainly radiotherapy+temozolomide) regimens against melanoma and GBM, respectively, remained stagnant around or below 10% [12,78]. For melanoma, DC-vaccines could not breach this 10%-ORR 'barrier' [12], which was eventually achieved by ICIs ( Supplementary Table S1) [67].…”