UTRECHT: MYELOMA IMMUNOTHERAPY

Immunotherapy of Myeloma and other haematological tumors printPrint Laat de tekst voorlezen met ReadSpeakerLees voor Immunotherapy of Myeloma and other haematological tumors Myeloma and several other haematological cancers can be treated by cellular immunotherapy, as illustrated by the success of allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) to induce long term remissions in a fraction of patients. This donor T-cell-mediated therapeutic Graft-vs-Tumor effect (GvT) is, however, frequently inefficiently developed, compromised by several tumor microenvironment-related immune escape mechanisms and is furthermore associated with severe complications such as Graft-vs-Host Disease (GvHD). Set out to improve the efficacy and safety of immune therapies of myeloma and other haematological malignancies, the research in the haemato-oncology group is focused on three important areas: 1. Separating GvT and GvHD by: a) Identification of GvT-associated Tumor antigens and minor Histocompatibility antigens (mHag) by Genome wide genetic association analyses (GWAS) and by reverse immunology. b) Development and clinical application therapeutic dendritic cell vaccines loaded with GvT associated mHags. c) Development and clinical application adoptive immunotherapy strategies based on GvT associated mHags. d) Defining the appropriate conditions to separate GvT from GvHD using regulatory T cells. e) Development of effective cancer vaccines by protein misfolding. 2. Understanding and eliminating tumor microenvironment-related immune escape mechanisms. a) Identification, in vitro and in vivo modulation of (intra) cellular mechanisms of immune suppression and immune resistance within the bone marrow, the natural microenvironment of myeloma microenvironment. Specific attention is given to p53, Notch and WNT signalling pathways. b) identification and modulation of (intra) cellular immune suppressive/resistance mechanisms leading to extramedullar Myeloma outgrowth. 3. Development of efficient targeted antibody therapy for MM by combining novel therapeutic antibodies with immune stimulatory agents like lenalidomide, pomalidomide, bortezomib and others. The research mission of Haemato-oncology lab is strongly linked to the clinical goals of the Department of Haematology, which is one of the largest SCT centres in the Netherlands and functions as a reference centre for Multiple Myeloma (MM) patients. The preclinical research is carried out in advanced in vitro models as well as in humanized in vivo murine models that are developed with a longstanding collaboration with Dr. A.C.M. Martens. Faculty Dr. Tuna Mutis Prof. dr. Henk Lokhorst Recent publications - Groen, R.W., W.A. Noort, R.A. Raymakers, H.J. Prins, L. Aalders, F.M. Hofhuis, P. Moerer, J.F. van Velzen, A.C. Bloem, B. van Kessel, H. Rozemuller, E. van Binsbergen, A. Buijs, H. Yuan, J.D. de Bruijn, M. de Weers, P.W. Parren, J.J. Schuringa, H.M. Lokhorst, T. Mutis, and A.C. Martens (2012). Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma. Blood 120, e9-e16. - Kneppers, E. B. van der Holt, M.J. Kersten, S. Zweegman, E. Meijer, G. Huls, J.J. Cornelissen, J.J. Janssen, C. Huisman, P.B. Cornelisse, C.P. Bruijnen, M. Emmelot, P. Sonneveld, H.M. Lokhorst, T. Mutis, M.C. Minnema –(2011) Lenalidomide maintenance following non-myeloablative allogeneic stem cell transplantation in multiple myeloma is not feasible: results of the HOVON 76 trial. Blood 118, 2413-2419 - Veer, M. van der, M. de Weers, B. van Kessel, J.M. Bakker, S. Wittebol, P.W.H.I. Parren, H.M. Lokhorst, T. Mutis (2011) Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. Haematologica 96, 284-290

SYMPTOM DIAGNOSIS

http://www.smw.ch/content/smw-2013-13829 Review article | Published 19 September 2013, doi:10.4414/smw.2013.13829 Cite this as: Swiss Med Wkly. 2013;143:w13829 The last century of symptom-oriented research in emergency presentations – have we made any progress? Roland Bingisser, Christian Hans Nickel Emergency Department, University Hospital, Basel, Switzerland Summary This review is dedicated to the last century of symptom-oriented research, taking three symptom complexes as typical examples of medical progress, and focusing on emergency presentations. Landmark publications in each area are discussed, with an attempt to focus on the methods used to achieve major breakthroughs. In abdominal pain, progress was achieved over a century ago by correlating symptoms and surgical pathology. Most diagnoses were made by using the clinical tools elaborated with careful observation and clinical examination. Together with the later reported outcomes, surgeons had an early and powerful tool for symptom-oriented research. In dyspnoea, progress was achieved much later, as a universal definition had to be elaborated over decades by consolidating clinical research, predominantly symptom-pathology correlation, and experimental research, such as function testing and experiments with animals and humans. In nonspecific presentations in emergency situations, progress has been achieved only recently, most probably owing to the fact that elderly patients are presenting in steeply increasing numbers, and the hallmark of disease presentation in the elderly seems to be less specific symptoms and complaints. This may be caused by altered physiology, polymorbidity, polypharmacy and the multiple difficulties encountered when taking histories in the elderly. Taken together, symptom-oriented research has been an important contributor to medical progress in the last century. Though it may be challenged by image- and laboratory-oriented research, it will remain part of patient-centred research because the epidemiology of symptoms, their clinical outcomes and their diagnostic importance according to severity will be the basis for the diagnostic process.

SIEMENS: SYMBIA INTEVO

Siemens Symbia Intevo xSPECT, the difference between seeing and knowing Siemens Symbia Intevo's precise alignment of SPECT and CT enables accurate, consistent and reproducible quantification. Symbia Intevo¹ – the world's first xSPECT system – combines the high sensitivity of single-photon emission computed tomography (SPECT) with the high specificity of CT. Completely integrating data from both modalities, Symbia Intevo generates high resolution and, for the first time ever, quantitative images. Higher resolution frame of reference In conventional SPECT/CT imaging, the SPECT image has always been reconstructed using SPECT's low-fidelity frame of reference. For this reason, the CT resolution has been downgraded dramatically to the level of SPECT to enable the mechanical fusion of both datasets. Siemens' new xSPECT modality reconstructs both the SPECT and CT portions of the image using the high resolution CT frame of reference for precise, accurate alignment that facilitates the extraction and deep integration of medically relevant information. This ability is also the basis for differentiating between tissue boundaries in bone imaging. With the xSPECT Bone feature, physicians can provide additional support for detection and distinguishing between cancerous lesions and degenerative disorders. First truly quantitative SPECT Symbia Intevo's precise alignment of SPECT and CT provides physicians with essential volumetric information from the CT scan, enabling accurate, consistent and reproducible quantification – a numerical indication of a tumor's level of metabolic activity. With the xSPECT Quant feature, the physician can apply quantitative information to aid in the assessment of whether a patient's course of treatment has regressed, stabilized or grown – an assessment that is difficult to make with a purely visual assessment of the tumor. Reduced CT dose While Symbia Intevo uses more CT data than ever before, Siemens is still able to limit patient dose by offering combined applications to reduce exposure (CARE). Unique to Siemens, these applications include the CARE Dose4D technique, which can reduce patient CT radiation dose by up to 68 percent.² Increased productivity and throughput Symbia Intevo also offers applications to improve productivity and patient throughput. For example, Siemens' AUTOFORM collimator – a standard feature on Symbia Intevo – captures up to 26 percent more counts, or photons that are generated from radiotracer activity as compared to conventional collimators.² This increased number of counts potentially reduces image acquisition time for increased patient throughput. Learn more about the technology behind Symbia Intevo and the xSPECT modality here.