TY  - JOUR
A1  - Löhr, Mario
A1  - Molcanyi, Marek
A1  - Poggenborg, Jörg
A1  - Spuentrup, Elmar
A1  - Runge, Matthias
A1  - Röhn, Gabriele
A1  - Härtig, Wolfgang
A1  - Hescheler, Jürgen
A1  - Hampl, Jürgen A.
T1  - Intracerebral Administration of Heat-Inactivated Staphylococcus Epidermidis Enhances Oncolysis and Prolongs Survival in a 9L Orthotopic Gliosarcoma Model
JF  - Cellular Physiology and Biochemistry
N2  - Background/Aims: The association between postoperative infection and prolonged survival in high-grade glioma is still a matter of debate. Previously we demonstrated that the intracerebral (i.c.) injection of heat-inactivated staphylococcal epitopes (HISE) resulted in a well-defined infux of immunocompetent cells across the blood-brain barrier. The present study investigated the potential antitumoral effect of HISE-immunostimulation in an experimental glioma model. Methods: Wistar rats were intracerebrally implanted with 9L gliosarcoma cells (n=6), 9L cells mixed with HISE (n=12), or phosphate buffered saline (n=4). Tumor growth was measured by serial magnetic resonance imaging (MRI). After death due to the tumor burden, the brains were histopathologically assessed for inflammation and oncolysis. A toxicity assay was performed to quantify potential impairment of HISE on tumor cell growth in vitro. Results: Animals treated by HISE showed a significant increase in average survival and even complete regression of an already established mass in one case. Naïve 9L gliosarcomas failed to recruit significant numbers of systemic immune cells. In contrast, concomitant intracerebral HISE inoculation lead to a oncolysis and a distinct peri- and intratumoral infiltration of macrophages, CD8 and CD4 co-expressing T-lymphocytes in two thirds of the tumor-bearing animals. The toxicity screening showed HISE-mediated oncolysis to be ineffective ex vivo. Conclusion: This study describes a novel approach for combatting malignant glioma using inactivated staphylococci as potent immunomodulators. Our results provide an outline for investigating the strategic potential of bacteria as emerging future therapeutics.
KW  - Glioblastoma
KW  - Immunotherapy
KW  - Oncolysis
KW  - Staphylococcus
KW  - Immunostimulatory adjuvant
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96754
ER  -