First Line Standard Therapy of Glioblastoma Multiforme With or Without add-on Treatment With Trivax, an Anti-tumour Immune Therapy Based on Tumour-lysate Charged Dendritic Cells

Vaccination represents a success story in modern medicine and its principles have been found to be valid in different species, at least in the case of infectious diseases. As of today, there is little reason to believe that this would not be true in the case of tumours. It is now generally acknowledged that human tumours carry a mutational antigenic (non-self) repertoire of immunogenic potential that may be a suitable target for antitumour immune therapy. During the last years accumulating evidence from mouse experiments indicates that one can immunise prophylactically against cancers as effectively as against an infectious agent. However, in contrast to most experimental mouse tumour models, human tumours have in general been within their host for a long time and thus had the opportunity to influence their microenvironment and the larger immunological environment. Antigens capable of mediating specific rejection were found in human as well as in mouse tumours.

Many of the clinical trials using dendritic cell (DC) -based cancer vaccination techniques were designed for the treatment of melanoma. Other important diseases in which DC-based cancer vaccination was studied include prostate cancer, B cell lymphoma, renal cell carcinoma, glioma and glioblastoma, breast and ovarian cancer, gastrointestinal cancer, and selected solid paediatric tumours. In most of these trials some in vivo and/or in vitro evidence for the generation of anti-tumour immunity was found and even complete or partial remission of the tumour was observed in selected cases. The first phase III trial demonstrating the efficacy of DC cancer vaccination for the treatment of prostate cancer was reported recently (www.dendreon.com). Also patients suffering from glioblastoma multiforme appear to benefit from DC cancer immune therapy. The side effects observed in DC cancer vaccinations were usually described to be mild and not limiting the application.

We developed a DC cancer vaccine technology, Trivax, advancing the design of DC cancer immune therapy in one critical aspect. It is the first such vaccine that is enable for releasing the immune modulatory cytokine interleukin (IL) -12. Trivax is comprised of IL-12 secreting DCs and a mixture of protein tumour antigens derived from the individual patient's tumour cells. No synthetic tumour antigen component is involved. Both components of Trivax are derived from the individual patient and are used for the treatment of only this patient. Trivax therefore represents a fully individualised somatic cell therapy medicine. Trimed's early clinical evaluations in patients suffering from kidney cancer, prostate cancer, bone tumours, and malignancies of childhood have confirmed the safety and the feasibility of the Trivax technology.

Glioblastoma multiforme (GBM) (ICD-O M9440/3) is the most malignant astrocytic tumour, composed of poorly differentiated neoplastic astrocytes. Histopathological features include cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, micro-vascular proliferation and necrosis. GBM typically affects patients of various age beginning in childhood and up to high age. It is preferentially located in the cerebral hemispheres. GBM may develop from diffuse astrocytomas WHO grade II or anaplastic astrocytomas (secondary GBM), but more frequently, they manifest after a short clinical history de novo, without evidence of a less malignant precursor lesion (primary GBM). In spite of modern oncological treatment, the prognosis of GBM remains dismal, with a median survival of little over 1 year.

GBM-Vax is a randomised, open-label, 2-arm, multi-centre, phase II clinical study with both groups undergoing surgery and receiving standard therapy with Temozolomide and radiotherapy; and the treatment group that in addition to the standard therapy receives cancer immune therapy with Trivax. Our aim is to extend therapy options presently including surgery, irradiation and Temozolomide with DC cancer vaccination to improve the poor prognosis of patients with GBM.