DCVax-L (autologous dendritic cell vaccine leaded with autologous tumor cell lysate)

Immunotherapy in high-grade glioma remains investigational, with randomized evidence to date demonstrating limited benefit for routine checkpoint inhibition in both newly diagnosed and recurrent disease. Selected vaccine and adoptive cellular strategies have shown encouraging survival signals in defined contexts, particularly when integrated following maximal safe resection. Persistent biological barriers, including tumor heterogeneity, antigen escape, low tumor mutational burden, and an immunosuppressive environment, continue to constrain durable responses. Future progress will depend on biologically informed trial design, optimized delivery strategies, and careful patient selection to ascertain the potential efficacy of immunotherapy in treating GBM.

Vaccines such as DCVax-L and oncolytic viruses including G47Δ have demonstrated promising outcomes in the clinical studies...The future research can focus on highlighting the complicated connections between the immune system and GBM, utilizing perspectives from preclinical models and clinical studies to formulate more effective and customized treatment options. This review emphasizes on the recent research results and clinical data, providing insights into prospective developments in GBM immunotherapy and highlighting the necessity of a comprehensive strategy to enhance patient outcomes.

Several whole-cell vaccine platforms (e.g., DCVax-L, CMV-targeted vaccines, and Cancer Transplant Immune Recognition Therapy (CTITR)) provide personalized formulations...Clinical observations indicate that cell-based vaccine preparations can be effective in both newly diagnosed glioblastoma patients treated post-surgery and in patients with recurrent gliomas. Cell-based vaccines, including CTITR, offer novel, antigen-agnostic immunotherapeutic platforms that harness autologous DC and autologous and allogeneic glioma cells, and their lysates bypass the need for predefined tumor-specific antigen selection.

We designed a multiphase combined treatment using subsequentially 1/ modulated electrohyperthermia and Newcastle Disease Virus therapy to induce immunogenic cell death (ICD) during temozolomide maintenance chemotherapy, 2/ two autologous DC vaccinations (IO-Vac®), and 3/ ICD immunotherapy, long-peptide vaccines and one boost IO-Vac® vaccine. TTF improved the OS in both unmeth and meth patients (17m/27% and 32m/59%), while DCvax®-L improved OS only in meth patients (15m/19% and 30m/58%). These real world data support to prospectively explore the addition of individualized multimodal immunotherapy during and after standard of care, and the role of treatment adaptations during treatment.

The results of the phase III clinical trial of DCVax-L (autologous tumor lysate-loaded dendritic cell vaccination), which has been shown to increase both median survival and long-term survival in newly diagnosed and relapsed glioblastoma, have been enthusiastically received by the scientific community. However, this study deserves some reflections regarding methodological issues related to the primary endpoint change, the long accrual period, and the suboptimal validity of the external control population used as the comparison arm.

Multiparametric MRI-based prediction model can assess treatment response to DCVax-L in patients with glioblastoma.

Dendritic cell vaccination remains a promising approach for GBM. It is therefore disappointing that due to key methodological limitations, the DCVax-L trial ultimately failed to provide sound conclusions about the potential efficacy of such approach for patients with glioblastoma.