Table 3.

Emerging GBM treatments under clinical trial investigation.

Intervention	Mechanism	Clinical trials/ongoing studies	Advantages	Disadvantages
Ipilimumab (Yervoy)	Monoclonal antibody targeting CTLA-4, enhances immune response	NCT02017717 NCT02311920	Potential to be non-cancer-type specific	Potential severe immunogenic adverse events Success is patient specific depending on the tumor’s mutations and antigen profile
Nivolumab (Opdivo)	Monoclonal antibody targeting PD-1, enhances immune response	NCT02017717 NCT02311920 NCT02667587 NCT02617589 NCT02658981 NCT02335918 NCT02327078	Potential to be non-cancer-type specific Amenable for use in combination approaches	Side effects include severe inflammation of organs
Heat shock protein peptide complex-96 vaccine	Vaccine with peptides that bind proteins involved in antigen- presenting pathway, creating an antitumor immune response	NCT02722512 NCT01814813 NCT00905060 NCT00293423	Efficient production, storage, and distribution Specific targeting of tumor cells	Only a small population of GBM patients would be eligible, due to the requirement of patients having undergone complete surgical resection before treatment The vaccine is created from the patient’s tumor tissue, leading to a potential delay in administration of treatment
Anti-EGFRvIII CAR-T- cell therapy	Adoptive cellular therapy, CAR-T cells recognize EGFRvIII tumor antigens and activate an anti- tumor response	NCT02664363 NCT02209376 NCT03283631 NCT01454596	Ability to target-specific cells, without antigen presentation via MHC 1	Potential severe immunogenic adverse effects Only useful against known antigens Time of production can be limiting
Natural killer (NK) cell therapy	Autologous NK cell infusions use patient-derived, activated lymphocytes to create an antitumor immune response	NCT00005813 NCT00003067	Targets the tumor cells without needing to identify specific antigens on the tumor cell Short expansion time	Expansion of NK cells on a large scale is difficult Risk of graft-versus-host disease, even with well- matched donors Nonspecific killing of cells
Rindopepimut (Rintega)	Peptide vaccine targeting the EGFRvIII deletion mutation	NCT01480479 NCT01498328 NCT00458601	Target-specific tumor cells	May only affect a portion of tumor cells with the targeted mutation
Dendritic cell (DC) vaccines	Autologous DCs are treated with tumor lysates and reintroduced to stimulate the immune system	NCT01808820 NCT00323115 NCT02010606 NCT01957956 NCT01204684 NCT03014804 NCT00639639	Large-scale isolation and expansion of DCs are feasible, taken from peripheral blood of the patient Tumor–antigen pulsed DCs can stimulate immune effector cells potently and rapidly	Cost of treatment can be prohibitive due to complex vaccine design No consensus yet on preferred target molecules