Therapeutic Immunization against Glioblastoma

Abstract

Glioblastoma is the most common form of brain cancer in adults that produces severe damage to the brain leading to a very poor survival prognosis. The standard of care for glioblastoma is usually surgery, as well as radiotherapy followed by systemic temozolomide chemotherapy, resulting in a median survival time of about 12 to 15 months. Despite these therapeutic efforts, the tumor returns in the vast majority of patients. When relapsing, statistics suggest an imminent death dependent on the size of the tumor, the Karnofsky Performance Status, and the tumor localization. Following the standard of care, the administration of Bevacizumab, inhibiting the growth of the tumor vasculature, is an approved medicinal treatment option approved in the United States, but not in the European Union, as well as the recently approved alternating electric fields (AEFs) generator NovoTTF/Optune. However, it is clear that regardless of the current treatment regimens, glioma patients continue to have dismal prognosis and novel treatments are urgently needed. Here, we describe different approaches of recently developed therapeutic glioma brain cancer vaccines, which stimulate the patient's immune system to recognize tumor-associated antigens (TAA) on cancer cells, aiming to instruct the immune system to eventually attack and destroy the brain tumor cells, with minimal bystander damage to normal brain cells. These distinct immunotherapies may target particular glioma TAAs which are molecularly defined, but they may also target broad patient-derived tumor antigen preparations intentionally evoking a very broad polyclonal antitumor immune stimulation.

Keywords: allogenic; autologous; brain tumor; glioma tumor; immunotherapy; therapeutic vaccine.

Figure 1

Time schedule of administrations of the treatment. Cyclocphosphamide (CY). ERC1671 doses A, B, C are allogeneic components. ERC1671 doses D are autologous components. Cycle 1 starts on day 1 (D1) with CY administration. ERC1671 is administered on day 6 (D6) with ERC1671 A, day 9 with ERC1671 D, day 13 with ERC1671 B, day 16 with ERC1671 C and day 20 (D20) with ERC1671 D.

Figure 2

Results obtained from patients treated under compassionate/single-name program. Although data need to be confirmed in a stringent clinical trial, results show a highly significant (log rank test, *** p-value = 0.0001) increase of the overall survival (OS) of late stage relapsing patients when treated with Gliovac when compared to historic control patients (study published by Barker et al., 1998 [32]).