Cellular-Based Immunotherapies for Patients with Glioblastoma Multiforme

Figure 2

Adoptive immunotherapy for GBM patients with CMV or GAA peptides. CMV and GAAs are highly expressed in GBM, but neither in healthy brain tissue, nor in nonmalignant brain tumors. Therefore, GAAs constitute good targets for immunotherapy of GBM patients. The streptamer technology offers the advantage of selecting CMV- or GAA-specific CD8⁺ CTLs at the good manufacturing practice (GMP) level in vitro. PBMCs from healthy donors are collected and isolated by streptamer beads. Noninduced antigen-specific T cells are purified and accumulated through a magnetic field and released by D-biotin from the streptamer complex. Subsequently, these cells are administered to the GBM patient. CMV/GAA-specific cytotoxic T cells can recognize the target antigens which are presented on the surface of GBM cells or GSCs. Cytotoxicity is exerted directly through the Fas or perforin pathway and/or indirectly by the release of cytokines. CMV: cytomegalovirus; GAA: glioblastoma associated antigen; GBM: glioblastoma multiforme; GSCs: glioblastoma stem cells; HD: healthy donor; PBMC: peripheral blood mononuclear cells; Pt: patient.