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 - TY - JOUR A1 - Prelog, Martina T1 - Vaccination in Patients with Rheumatoid Arthritis Receiving Immunotherapies JF - Clinical & Cellular Immunology N2 - Patients with rheumatoid arthritis (RA) are at higher risk to suffer from morbidity due to vaccine-preventable diseases and, thus, display an important target population to receive vaccines for protection from infectious complications. There have been only a few studies focusing on the administration of vaccines in RA patients with immunotherapy. Overall, antibody response rates against influenza or pneumococcal disease appeared to be only slightly lower than expected in healthy individuals. Crucial problems in the interpretation of data from studies in RA patients vaccinated against influenza and pneumococcal disease are the impaired comparability of studies due to different study designs and type of vaccines used, different health states among RA patients, heterogeneity in treatments including concomitant therapy with conventional DMARDs and glucocorticoids in addition to biological agents. Assessment of vaccination status should be performed in the initial work-up of patients with RA and should ideally be administered before initiation of immunotherapies or during stable disease. Due to differences in antibody responses and uncertainty regarding maintenance of protective antibodies, routine controls for antibody titers and specific strategies for earlier re-vaccination might be scheduled for patients with RA. KW - Immunotherapy KW - Anti-TNF-alpha agents KW - Rituximab KW - Tocilizumab KW - Abatacept KW - Pneumococcal vaccination KW - Influenza vaccination Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96446 ER - TY - JOUR A1 - Stoevesandt, Johanna A1 - Hofmann, Bernd A1 - Hain, Johannes A1 - Kerstan, Andreas A1 - Trautmann, Axel T1 - Single venom-based immunotherapy effectively protects patients with double positive tests to honey bee and Vespula venom JF - Allergy, Asthma & Clinical Immunology N2 - Background Referring to individuals with reactivity to honey bee and Vespula venom in diagnostic tests, the umbrella terms “double sensitization” or “double positivity” cover patients with true clinical double allergy and those allergic to a single venom with asymptomatic sensitization to the other. There is no international consensus on whether immunotherapy regimens should generally include both venoms in double sensitized patients. Objective We investigated the long-term outcome of single venom-based immunotherapy with regard to potential risk factors for treatment failure and specifically compared the risk of relapse in mono sensitized and double sensitized patients. Methods Re-sting data were obtained from 635 patients who had completed at least 3 years of immunotherapy between 1988 and 2008. The adequate venom for immunotherapy was selected using an algorithm based on clinical details and the results of diagnostic tests. Results Of 635 patients, 351 (55.3%) were double sensitized to both venoms. The overall re-exposure rate to Hymenoptera stings during and after immunotherapy was 62.4%; the relapse rate was 7.1% (6.0% in mono sensitized, 7.8% in double sensitized patients). Recurring anaphylaxis was statistically less severe than the index sting reaction (P = 0.004). Double sensitization was not significantly related to relapsing anaphylaxis (P = 0.56), but there was a tendency towards an increased risk of relapse in a subgroup of patients with equal reactivity to both venoms in diagnostic tests (P = 0.15). Conclusions Single venom-based immunotherapy over 3 to 5 years effectively and long-lastingly protects the vast majority of both mono sensitized and double sensitized Hymenoptera venom allergic patients. Double venom immunotherapy is indicated in clinically double allergic patients reporting systemic reactions to stings of both Hymenoptera and in those with equal reactivity to both venoms in diagnostic tests who have not reliably identified the culprit stinging insect. KW - Anaphylaxis KW - Double sensitization KW - Field sting KW - Honey bee KW - Hymenoptera venom KW - Immunotherapy KW - Relapse KW - Risk factor KW - Treatment failure KW - Vespula Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96808 UR - http://www.aacijournal.com/content/9/1/33 ER -