@article{DanhofRascheMottoketal.2021, author = {Danhof, Sophia and Rasche, Leo and Mottok, Anja and Steinm{\"u}ller, Tabea and Zhou, Xiang and Schreder, Martin and Kilian, Teresa and Strifler, Susanne and Rosenwald, Andreas and Hudecek, Michael and Einsele, Hermann and Gerhard-Hartmann, Elena}, title = {Elotuzumab for the treatment of extramedullary myeloma: a retrospective analysis of clinical efficacy and SLAMF7 expression patterns}, series = {Annals of Hematology}, volume = {100}, journal = {Annals of Hematology}, number = {6}, issn = {1432-0584}, doi = {10.1007/s00277-021-04447-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266468}, pages = {1537-1546}, year = {2021}, abstract = {Extramedullary disease (EMD) represents a high-risk state of multiple myeloma (MM) associated with poor prognosis. While most anti-myeloma therapeutics demonstrate limited efficacy in this setting, some studies exploring the utility of chimeric antigen receptor (CAR)-modified T cells reported promising results. We have recently designed SLAMF7-directed CAR T cells for the treatment of MM. SLAMF7 is a transmembrane receptor expressed on myeloma cells that plays a role in myeloma cell homing to the bone marrow. Currently, the only approved anti-SLAMF7 therapeutic is the monoclonal antibody elotuzumab, but its efficacy in EMD has not been investigated thoroughly. Thus, we retrospectively analyzed the efficacy of elotuzumab-based combination therapy in a cohort of 15 patients with EMD. Moreover, since the presence of the target antigen is an indispensable prerequisite for effective targeted therapy, we investigated the SLAMF7 expression on extramedullary located tumor cells before and after treatment. We observed limited efficacy of elotuzumab-based combination therapies, with an overall response rate of 40\% and a progression-free and overall survival of 3.8 and 12.9 months, respectively. Before treatment initiation, all available EMD tissue specimens (n = 3) demonstrated a strong and consistent SLAMF7 surface expression by immunohistochemistry. Furthermore, to investigate a potential antigen reduction under therapeutic selection pressure, we analyzed samples of de novo EMD (n = 3) outgrown during elotuzumab treatment. Again, immunohistochemistry documented strong and consistent SLAMF7 expression in all samples. In aggregate, our data point towards a retained expression of SLAMF7 in EMD and encourage the development of more potent SLAMF7-directed immunotherapies, such as CAR T cells.}, language = {en} } @article{StijnisDijkmansBartetal.2015, author = {Stijnis, Kees and Dijkmans, Anneke C. and Bart, Aldert and Brosens, Lodewijk A. A. and Muntau, Birgit and Schoen, Christoph and Barth, Thomas F. and van Gulik, Thomas and van Gool, Tom and Grobusch, Martin P. and Tappe, Dennis}, title = {Echinococcus vogeli in Immigrant from Suriname to the Netherlands}, series = {Emerging Infectious Diseases}, volume = {21}, journal = {Emerging Infectious Diseases}, number = {3}, doi = {10.3201/eid2103.141205}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143953}, pages = {528-530}, year = {2015}, language = {en} } @article{ThiryScheerGoessens1988, author = {Thiry, Marc and Scheer, Ulrich and Goessens, Guy}, title = {Localization of DNA within Ehrlich tumour cells nucleoli by immunoelectron microscopy}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-39327}, year = {1988}, abstract = {The distribution of DNA in Ehrlich tumour cell nucleoli was investigated by means of an immunocytochemical approach , involving a monoclonal antibody directed against double- and single-stranded DNA. Immunolabelling was performed . either before or after the embedding process. The postembedding labelling method allows better ultrastructural preservation than the preembedding labelling method. In particular, the various nucleolar components are well preserved and identifiable. In the nucleolus, labelling is particularly concentrated over the perinucleolar chromatin and over its intranucleolar invaginations, which penetrate the nucleolar body and often terminate at the fibrillar centres. In addition, aggregates of gold particles are found in the fibrillar centres, preferentially towards the peripheral regions. By contrast, the dense fibrillar component is completely devoid of labelling. The results seem to indicate that DNA containing the rDNA genes is located in the fibrillar centres, with a preference for the peripheral regions. This finding suggests that transcription of the rDNA genes should occur within the confines of the fibrillar centre, probably close to the boundary region of the surrounding dense fibrillar component. The results are discussed in the light of present knowledge of the functional organization of the nucleolus.}, language = {en} }