The Safety of available immunotherapy for the treatment of glioblastoma

Abstract

Introduction Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Current standard of care involves maximal surgical resection combined with adjuvant chemoradiation. Growing support exists for a role of immunotherapy in treating these tumors with the goal of targeted cytotoxicity. Here we review data on the safety for current immunotherapies being tested in GBM. Areas covered Safety data from published clinical trials, including ongoing clinical trials were reviewed. Immunotherapeutic classes currently under investigation in GBM include various vaccination strategies, adoptive T cell immunotherapy, immune checkpoint blockade, monoclonal antibodies, and cytokine therapies. Trials include children, adolescents, and adults with either primary or recurrent GBM. Expert commentary Based on the reviewed clinical trials, the current immunotherapies targeting GBM are safe and well-tolerated with minimal toxicities which should be noted. However, the gains in patient survival have been modest. A safe and well-tolerated combinatory immunotherapeutic approach may be essential for optimal efficacy towards GBM.

Glioblastoma Treatments: An Account of Recent Industrial Developments

“…At the same time, there has been a real surge in the number of publications related to this topic (from 15 in 1999 to 164 in 2017 according to pubmed). The reader is redirected toward the large number of excellent reviews on this topic (Calinescu et al, 2015 ; Binder et al, 2016 ; Desaia et al, 2016 ; Hodges et al, 2016 ; Kamran et al, 2016 ; Dunn-Pirio and Vlahovic, 2017 ; Farber et al, 2017 ; Lyon et al, 2017 ; McGranahan et al, 2017 ; Miyauchi and Tsirka, 2017 ; Sahebjam et al, 2017 ; Tivnan et al, 2017 ), providing details about current or past clinical trials (Binder et al, 2016 ), and the different modes of action of these treatments (Calinescu et al, 2015 ; Curry and Lim, 2015 ).…”

Immunotherapy for Glioblastomas

“…As such, CAR T cells recognize target antigens without a need for MHC peptide presentation, circumventing one major mechanism of tumor immune escape-MHC downregulation. CAR T-cell therapy has demonstrated promising results and FDA approval for hematological malignancy is expected shortly [11].…”

A concise review of immunotherapy for glioblastoma

“…While TSAs have a greater potential to evoke a more potent and specific immune response compared to TAAs, they are exceedingly rare. EGFRvIII, IDH-1/2 mutations (e.g., R132H), and CMV proteins are known TSAs expressed in GB and IL-13Rα2, HER-2, gp100, survivin, WT1, TRP2, EphA2, SOX2, SOX11, MAGE-A1, MAGE-A3, AIM2, SART1, and tenascin are TAAs expressed in GB [10] . Heterogeneity of GBs warrants the demand for individualized, patient-specific and non-toxic immunotherapies.…”

“…This strategy is a targeted approach including the direct administration of a selected protein or peptide antigen frequently used with an adjuvant such as keyhole limpet hemocyanin (KLH) to enhance the immunogenicity [10,40,41] .…”

“…Cytokines are secreted or membrane-bound proteins and potent immunomodulators with a critical role in immune system coordination [10][11][12][13] . Anti-tumor activities of cytokines have been reported in animal studies paving the way for consequent cytokine-based cancer treatment strategies.…”