@article{WeberGlutschGeissingeretal.2020, author = {Weber, J. and Glutsch, V. and Geissinger, E. and Haug, L. and Lock, J.F. and Schneider, F. and Kneitz, H. and Goebeler, M. and Schilling, B. and Gesierich, A.}, title = {Neoadjuvant immunotherapy with combined ipilimumab and nivolumab in patients with melanoma with primary or in transit disease}, series = {British Journal of Dermatology}, volume = {183}, journal = {British Journal of Dermatology}, number = {3}, doi = {10.1111/bjd.18739}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213520}, pages = {559-563}, year = {2020}, abstract = {The introduction of new therapeutic agents has revolutionized the treatment of metastatic melanoma. The approval of adjuvant anti-programmed death-1 monotherapy with nivolumab or pembrolizumab, and dabrafenib plus trametinib has recently set a new landmark in the treatment of stage III melanoma. Now, clinical trials have shown that immune checkpoint blockade can be performed in a neoadjuvant setting, an approach established as a standard therapeutic approach for other tumour entities such as breast cancer. Recent studies suggest that a pathological response achieved by neoadjuvant immunotherapy is associated with long-term tumour control and that short neoadjuvant application of checkpoint inhibitors may be superior to adjuvant therapy. Most recently, neoadjuvant ipilimumab plus nivolumab in stage III melanoma was reported. With two courses of dose-optimized ipilimumab (1 mg kg-1) combined with nivolumab (3 mg kg-1), pathological responses were observed in 77\% of patients, while only 20\% of patients experienced grade 3 or 4 adverse events. However, the neoadjuvant trials employing combined immune checkpoint blockade conducted so far have excluded patients with in transit metastases, a common finding in stage III melanoma. Here we report four patients with in transit metastases or an advanced primary tumour who have been treated with neoadjuvant ipilimumab plus nivolumab according to the OpACIN-neo trial scheme (arm B). All patients achieved radiological disease control and a pathological response. None of the patients has relapsed so far.}, language = {en} } @article{StoevesandtHofmannHainetal.2013, author = {Stoevesandt, Johanna and Hofmann, Bernd and Hain, Johannes and Kerstan, Andreas and Trautmann, Axel}, title = {Single venom-based immunotherapy effectively protects patients with double positive tests to honey bee and Vespula venom}, series = {Allergy, Asthma \& Clinical Immunology}, journal = {Allergy, Asthma \& Clinical Immunology}, doi = {10.1186/1710-1492-9-33}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96808}, year = {2013}, abstract = {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.}, language = {en} } @article{Prelog2013, author = {Prelog, Martina}, title = {Vaccination in Patients with Rheumatoid Arthritis Receiving Immunotherapies}, series = {Clinical \& Cellular Immunology}, journal = {Clinical \& Cellular Immunology}, doi = {10.4172/2155-9899.S6-007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96446}, year = {2013}, abstract = {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.}, language = {en} } @article{LoehrMolcanyiPoggenborgetal.2013, author = {L{\"o}hr, Mario and Molcanyi, Marek and Poggenborg, J{\"o}rg and Spuentrup, Elmar and Runge, Matthias and R{\"o}hn, Gabriele and H{\"a}rtig, Wolfgang and Hescheler, J{\"u}rgen and Hampl, J{\"u}rgen A.}, title = {Intracerebral Administration of Heat-Inactivated Staphylococcus Epidermidis Enhances Oncolysis and Prolongs Survival in a 9L Orthotopic Gliosarcoma Model}, series = {Cellular Physiology and Biochemistry}, journal = {Cellular Physiology and Biochemistry}, doi = {10.1159/000350081}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96754}, year = {2013}, abstract = {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. Na{\"i}ve 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.}, language = {en} } @article{GoncharovaRuzhenkovaPetrovetal.2016, author = {Goncharova, Elena P. and Ruzhenkova, Julia S. and Petrov, Ivan S. and Shchelkunov, Sergey N. and Zenkova, Marina A.}, title = {Oncolytic virus efficiency inhibited growth of tumour cells with multiple drug resistant phenotype in vivo and in vitro}, series = {Journal of Translational Medicine}, volume = {14}, journal = {Journal of Translational Medicine}, number = {241}, doi = {10.1186/s12967-016-1002-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165714}, pages = {1-14}, year = {2016}, abstract = {Background Tumour resistance to a wide range of drugs (multiple drug resistant, MDR) acquired after intensive chemotherapy is considered to be the main obstacle of the curative treatment of cancer patients. Recent work has shown that oncolytic viruses demonstrated prominent potential for effective treatment of diverse cancers. Here, we evaluated whether genetically modified vaccinia virus (LIVP-GFP) may be effective in treatment of cancers displaying MDR phenotype. Methods LIVP-GFP replication, transgene expression and cytopathic effects were analysed in human cervical carcinomas KB-3-1 (MDR-), KB-8-5 (MDR+) and in murine melanoma B-16 (MDR-), murine lymphosarcomas RLS and RLS-40 (MDR+). To investigate the efficacy of this therapy in vivo, we treated immunocompetent mice bearing murine lymphosarcoma RLS-40 (MDR+) (6- to 8-week-old female CBA mice; n = 10/group) or melanoma B-16 (MDR-) (6- to 8-week-old female C57Bl mice; n = 6/group) with LIVP-GFP (5 × 107 PFU of virus in 0.1 mL of IMDM immediately and 4 days after tumour implantation). Results We demonstrated that LIVP-GFP replication was effective in human cervical carcinomas KB-3-1 (MDR-) and KB-8-5 (MDR+) and in murine melanoma B-16 (MDR-), whereas active viral production was not detected in murine lymphosarcomas RLS and RLS-40 (MDR+). Additionally, it was found that in tumour models in immunocompetent mice under the optimized regimen intratumoural injections of LIVP-GFP significantly inhibited melanoma B16 (33 \% of mice were with complete response after 90 days) and RLS-40 tumour growth (fourfold increase in tumour doubling time) as well as metastasis. Conclusion The anti-tumour activity of LIVP-GFP is a result of direct oncolysis of tumour cells in case of melanoma B-16 because the virus effectively replicates and destroys these cells, and virus-mediated activation of the host immune system followed by immunologically mediated destruction of of tumour cells in case of lymphosarcoma RLS-40. Thus, the recombinant vaccinia virus LIVP-GFP is able to inhibit the growth of malignant cells with the MDR phenotype and tumour metastasis when administered in the early stages of tumour development.}, language = {en} }