Vascular endothelia growth factor targeted therapy may improve the effect of dendritic cell-based cancer immune therapy

Efficacy and safety analysis on dendritic cell-based vaccine-treated high-grade glioma patients: a systematic review and meta-analysis

“…Of these, 25 studies were excluded because they were not appropriately controlled, and four other studies were excluded due to absence of data for analysis. Eventually, three RCTs 18 – 20 and ten NRS, including five non-randomized controlled trials, 21 – 25 four historically controlled studies, 26 – 29 and one cohort study, 30 involving 307 DC-vaccinated (DC group) and 637 non-DC-vaccinated (CT group: control therapy group) patients, were included in the meta-analysis. The detailed selection process was described in Figure 1 , according to the PRISMA Statement for reviews and meta-analysis.…”

New Directions in Anti-Angiogenic Therapy for Glioblastoma

“…Despite the conventional notion that the central nervous system is immune-privileged due to the blood brain barrier, the immunomodulatory effect of anti-VEGF has led to recent clinical trials combining bevacizumab with immunotherapy in hopes of a synergistic effect in facilitating anti-tumor immunity. Preliminary results from a phase 2 trial of standard of care chemoradiation versus standard of care plus the dendritic cell vaccine AV0113 in patients with newly diagnosed glioblastoma showed no difference in PFS or OS; however, in the subgroup of 22 patients that received the vaccine as second-line therapy with bevacizumab, there was an improvement in OS compared to the control arm (535 ± 155 days versus 406 ± 224 days) [118]. Preliminary results from the phase 2 study of patients with EGFRvIII mutant recurrent glioblastomas (approximately 20−30% of all primary glioblastomas) demonstrate that the combination of rindopepimut, a peptide vaccine against EGFRvIII, with bevacizumab prolonged median OS from 8.8 months in the control arm (bevacizumab plus keyhole limpet hemocyanin) to 12 months in the experimental arm [54].…”

Overview of Current Immunotherapeutic Strategies for Glioma

“…A randomized Phase II clinical trial using SOC with added antiangiogenic therapy with bevacizumab and DC vaccine (AVOH3), generated by priming DCs with autologous tumor antigens, showed an increase in median OS (535 days +/- 155) in the combined bevacizumab and vaccine group compared with the vaccine group (438 days +/- 205) or bevacizumab alone group (406 days +/- 224) [78], suggesting a possible mechanism of decreased immunosuppression induced by the anti-VEGF antibodies.…”

“…Results have shown that immunological approaches are generally safe, with minimal side effects and able to elicit specific immune responses and in some cases improve progression-free survival (PFS) and overall survival (OS) [77–85]. Studies employed gene therapy [86–93], DC vaccines, which vary primarily in the agents used to prime the DCs for antigen presentation: either GBM-associated antigens (GAA) [81,94], autologous tumor lysates [78,82,94–97] or RNA from GBM stem cells [85], with or without adjuvants aimed to activate Toll-like receptors (TLRs). A few trials tested the effect of antigenic stimulation with peptides or tumor cells [77,79,98–102] and some analyzed the effect of autologous T-cell transfer on eliciting an antiglioma immune response [103,104] or the effect of specific antibodies against GBM receptors or to deplete Tregs [105,106].…”