Immunotherapy of Malignant Gliomas Using Autologous and Allogeneic Tissue Cells

F.      M. Hofman; A.      Stathopoulos; C.      A. Kruse; T.      C. Chen; V.      E.J.C. Schijns

Abstract

Immunotherapy of brain tumors is rapidly emerging as a potential clinical option [1-3]. The quality and magnitude of immune responses evoked by the new generation anti-tumor vaccines is in general highly dependent on the source or choice of peptide antigens, and as well, a suitable immunopotentiator. Poorly immunogenic antigens, such as those present in tumor cell lysates, may not reliably provide stimulation like recombinant or DNA-encoded protein antigens might be expected to. In addition, the efficacy of the vaccine may depend on inherent counteracting measures of the tumor which dampen immune surveillance and immune effector activity triggered by immunization [4]. Our body has many means of limiting an immune response to our own (self) proteins. In particular, patients with gliomas exhibit a broad suppression of cell-mediated immunity [5-8]. Unfortunately, for most tumor vaccines the induction of local or systemic immune effector cells does not necessarily translate into objective clinical responses or increased survival [9]. Here we review immunotherapeutic approaches against gliomas and recent pre-clinical and clinical initiatives based on cellular or active immunization of the patients immune system using autologous and allogeneic tissues or cultured cells. Available evidence shows that single modality cancer therapies likely remain suboptimal. Combination regimens targeting the immune system at multiple coordinated levels must be developed, and possibly combined with strategies to inhibit immune suppressive factors if significant clinical benefit is to be achieved.

Keywords: Astrocytoma, allogeneic, biotherapy, brain tumor, CTL, glioma, immunotherapy, immunization, Malignant Gliomas, brain tumors, anti-tumor vaccines, immune surveillance, immune response, cell-mediated immunity, Glioblastoma multiforme, radiation, chemotherapy, pancytopenia, alkylating agent temozolomide, Coley's Toxins, tumor-specific cytotoxic T cells, class I Major Histocompatibility Complex, CD8-positive cytotoxic T cells, CD4 T cells, natural killer (NK) cells, Effector T Cells, T lymphocytes, Tumor Associated Antigens, glioma-associated antigens, real time polymerase chain reactions (qRT-PCR), tenascin, gp240, Antigen Presenting Cells, Dendritic cells, Dendritic Cell Vaccines, interferon (IFN)-α, Granulocyte macrophage-colony stimulating factor, toll-like receptor, CpG-oligonucleotide, K562 cells, IL-4-secreting fibroblasts, tumor-infiltrating immune cells, renal carcinoma, DNA-encoded protein antigens, Classical vaccines, tumor antigens, leukapheresis, synthetic CpG motifs, RNA oligonucleotides, oncolytic viruses, immunosuppression, immunosuppressive glucocorticoids, transforming growth factor (TGF)-β, interleukin, Vascular Endothelial Growth Factor, indoleamine 2,3, dioxgenase, T cell receptor, cytomegalovirus-specific T cells