Immunotherapeutic Approaches for Glioblastoma Treatment

Abstract

Glioblastoma remains a challenging disease to treat, despite well-established standard-of-care treatments, with a median survival consistently of less than 2 years. In this review, we delineate the unique disease-specific challenges for immunotherapies, both brain-related and non-brain-related, which will need to be adequately overcome for the development of effective treatments. We also review current immunotherapy treatments, with a focus on clinical applications, and propose future directions for the field of GBM immunotherapy.

rWTC‐MBTA Vaccine Induces Potent Adaptive Immune Responses Against Glioblastomas via Dynamic Activation of Dendritic Cells

“…[1] GBM poses a formidable challenge with the current standard of care for newly diagnosed GBM involving maximal surgical resection, followed by radiotherapy and temozolomide. [2] Despite this treatment, the median overall survival for GBM patients remains less than 15 months, underscoring the urgent need for novel therapeutics. [2] Among the arsenal of cancer immunotherapies, checkpoint inhibition through PD-1 (e.g., Cemiplimab, Nivolumab, and Pembrolizumab), PD-L1 (e.g., Atezolizumab, Avelumab, Durvalumab), and CTLA-4 (Ipilimumab) have shown promising efficacy against multiple metastatic cancers, including breast, melanoma, and lung cancers.…”

“…[2] Despite this treatment, the median overall survival for GBM patients remains less than 15 months, underscoring the urgent need for novel therapeutics. [2] Among the arsenal of cancer immunotherapies, checkpoint inhibition through PD-1 (e.g., Cemiplimab, Nivolumab, and Pembrolizumab), PD-L1 (e.g., Atezolizumab, Avelumab, Durvalumab), and CTLA-4 (Ipilimumab) have shown promising efficacy against multiple metastatic cancers, including breast, melanoma, and lung cancers. [3,4] However, the translation of checkpoint inhibitors to GBM was only effective in patients with mismatch repair deficiency.…”

“…[ 1 ] GBM poses a formidable challenge with the current standard of care for newly diagnosed GBM involving maximal surgical resection, followed by radiotherapy and temozolomide. [ 2 ] Despite this treatment, the median overall survival for GBM patients remains less than 15 months, underscoring the urgent need for novel therapeutics. [ 2 ]…”

“…[ 2 ] Despite this treatment, the median overall survival for GBM patients remains less than 15 months, underscoring the urgent need for novel therapeutics. [ 2 ]…”

A Window of Opportunity to Overcome Therapeutic Failure in Neuro-Oncology

“…3,4 It has also been recognized, however, that there is intratumoral heterogeneity in glioblastoma, that mutational burden in most glioblastoma tumors is relatively low, and that these tumors can promote a highly immunosuppressive tumor microenvironment that has contributed to the failure of all attempts to date to target these tumors with systemically administered immunomodulatory agents. 5,6 There remains an urgent need to develop novel glioblastoma-specific agents that will improve the survival of patients with this deadly disease.…”