Immunotherapy for glioma:  getting closer to the clinical arena?
OBJECTIVE
During recent years different approaches have been explored to raise effective antitumor responses against brain tumors and particularly glioblastomas (GBMs). In most cases, cancer vaccines were based on autologous dendritic cells loaded with GBM peptides or whole tumor lysates. Many phase I-II studies showed that such strategy is feasible and nontoxic but failed to provide convincing evidence of its efficacy. This was due to study design and other biological issues: local immune suppression and insufficient characterization of appropriate epitopes appear as particularly relevant.


RESULTS
In neuro-oncology intriguing data have been obtained by vaccinating patients with the epidermal growth factor receptor variant III (EGFRvIII) peptide, reproducing a specific epitope arising because of large deletion of the EGFR gene. In other cancers immunotherapy is obtaining clinically meaningful results: in prostate cancer vaccination with dendritic cells loaded with a cancer peptide, and in metastatic melanoma antibodies against an immune gate-keeper, CTL4, both led to increased survival and have been approved by FDA.


CONCLUSIONS
On the basis of these and other clinical and preclinical findings it appears that several approaches may have chances of clinical success. They include combinatorial treatments of chemotherapy and immunotherapy, systemic and local immunotherapy, vaccination against specific targets, for example cytomegalovirus protein or stem cell markers re-expressed during brain cancer progression.
Unit of Molecular Neuro-Oncology, Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, IFOM-IEO Campus, Milan, Italy. gaetano.finocchiaro@gmail.com
Gaetano
G
Finocchiaro
Serena
S
Pellegatta
D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology; D005910:Glioma / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology
D019496:Cancer Vaccines; D066246:ErbB Receptors