Wuerzburg University Hospital

“Currently 65 Antibodies Combinations Are Approved For Various Cancer Treatments” The treatment landscape for multiple myeloma ailment is a rapidly evolving field with ongoing research and clinical trials aimed at better understanding these conditions and developing effective therapies. Multiple myeloma is a group of hematological malignancies disorders characterized by the abnormalities in plasma cells, a type of white blood cell. With the rising incidence as well as prevalence of multiple myeloma year by year led to the development of novel combination therapies which can target these ailments. In the recent year, finding for the need of novel treatments led to the discovery of antibody combinations used for the treatment of multiple myeloma. The research and development of antibody combinations for the treatment of multiple myeloma begin when the monoclonal antibodies (mAbs), daratumumab (Darzalex) in addition elotuzumab (Empliciti), have aided to expand the treatment options for multiple myeloma and thereby led to great improvement in patient outcome. The mechanism used by these antibodies is to target the signaling lymphocytic activation molecule family 7 (SLAMF7)/ CD319 or CD38 that are frequently overexpressed in multiple myeloma cells. On the account of that reason, several antibody combinations, like Sarclisa (isatuximab-irfc), in combination with pomalidomide (Pomalyst) and dexamethasone, Sarclisa in combination with carfilzomib (Kyprolis) and dexamethasone, and Darzalex Faspro, Kyprolis, and Dexamethasone were approved in the 2020 and 2021 for the treatment of adult patients with relapsed or refractory multiple myeloma. Download Research Insight: Since the discovery of antibody combinations involved for the treatment of multiple myeloma, there has been significant research into understanding the mode of action of antibody has been completed. Studies have focused on developing treatments that can prevent the abnormal aggregation of plasma cells or mitigate its toxic effects. Succeeding the approval of antibody combination, many clinical as well as translational research are being initiated in the arena with the intention to develop and innovative and advanced antibody combination treatment regimen which will aid to provide treatment for numerous patients suffering from multiple myeloma malignancies. Currently, numerous clinical researches are ongoing in the realm, few of which have reached the late stage of development that are being conducted by various pharma companies and hospitals such as Sanofi, Pfizer, Wuerzburg University Hospital, ClinAssess GmbH, Arbeitsgemeinschaft medikamentoese Tumortherapie, SWOG Cancer Research Network, National Cancer Institute (NCI), ECOG-ACRIN Cancer Research Group, Eastern Cooperative Oncology Group, European Myeloma Network, Karyopharm Therapeutics, GlaxoSmithKline, Janssen Research & Development, Alexion Pharmaceuticals etc. Apart from the involvement of various stakeholders from the giant pharma companies, the pipeline for sphere of antibody combinations for the treatment of multiple myeloma consist of monoclonal and bispecific antibodies targeting immune checkpoint receptors like anti PD-1, anti PD-L1, anti CTLA-4 along with BCMA, CD3, OX40, CD38, GPRC5D directed CD3 bispecific antibodies, interleukin- 6 receptor mAbs along with gamma secretase inhibitor. Presence of different types of therapeutic agents with antibody illustrates that the realm of antibody combinations to treat multiple myeloma is growing and it is expected that multiple novel combinations will be launch in the upcoming years. The vista of antibody combination therapy for the treatment of multiple myeloma is expanding at an incredible gait on the account of the rising growth of antibody combinations in the commercial market along with augmenting partnerships, increasing research, investments and collaborations in the domain. For instance, in January 2024, a researcher at Penn State Cancer Institute based in the US, stated that the bispecific antibodies plays a significant role for the treatment of in hematologic malignancies, particularly multiple myeloma. Despite the fact that chimeric antigen receptor (CAR)-T cell therapy have made surplus benefits to patients, yet the role of bispecific antibodies becomes progressively apparent in the difficult-to-treat population with multiple myeloma patients. Antibody combinations represent a significant breakthrough in the management of multiple myeloma. By targeting the key pathway and receptors such as SLAMF7/ CD319 or CD38 that are involved in progression of multiple myeloma, the therapeutic approach offer an effective and convenient way to increase effectiveness and reduce the side effects along with drug resistances. Despite some challenges, Antibody combinations clenches great promise in transforming the lives of those suffering from multiple myeloma, providing a beacon of aspiration to numerous individuals suffering from multiple myeloma. As research continues, the use of antibody combination therapies may become more refined and accessible treatment, further improving their role in multiple myeloma management.

The glycoprotein V of the blood platelets is an important switch point for haemostasis and thrombus formation. This new finding could have great clinical potential. When our blood vessels are injured by cuts, abrasions, or bruises, it is vital that the bleeding is stopped, and the wound is sealed. This process is called hemostasis and involves two main components: First, blood platelets attach to the wound edges, form a plug and provisionally seal the injury. Secondly, blood coagulation or the coagulation cascade is initiated, leading to the formation of long fibrin fibers, which together with platelets seal the wound tightly. However, if fibrin is formed in excess, e.g. in chronic wounds, thrombosis and subsequent vascular occlusions can occur. Therefore, the strict regulation of fibrin formation is important. How blood clotting is limited was not fully understood until now. In an international project coordinated by the University Hospital of Würzburg, researchers have now deciphered a central regulatory mechanism of fibrin formation and propose new therapeutic approaches. The results have been published in the journal Nature Cardiovascular Research. GPV controls thrombin activity and fibrin formation In this study, the research group led by Professor Bernhard Nieswandt identified a fundamentally new mechanism: "For the first time, we were able to uncover a new switching point that regulates both hemostasis and thrombosis. This switch is glycoprotein V, GPV, which is expressed on the surface of blood platelets. GPV controls the activity of the enzyme thrombin, which is responsible for the formation of fibrin," explains Bernhard Nieswandt, head of the Institute of Experimental Biomedicine I and member of the board of the Rudolf Virchow Center -- Center for Integrative and Translational Bioimaging (RVZ) at the University of Würzburg. Thrombin is a crucial enzyme in blood clotting and its activity must therefore be precisely spatio-temporally controlled. Until now, it was known that the surface receptor GPV is cleaved by thrombin during platelet activation. This releases GPV as a soluble form. However, the physiological function of this receptor was largely unknown. Using genetic and pharmacological approaches, the researchers showed that thrombin-mediated cleavage of GPV limits fibrin formation. By remaining bound to thrombin, soluble GPV alters the activity of thrombin so that it can form less fibrin. "Findings will change textbook knowledge" In experimental thrombosis models, soluble GPV was shown to prevent, among other things, the formation of vaso-occlusive thrombi and to lead to a significant protection from experimental stroke and associated brain damage. Bernhard Nieswandt is convinced that these new findings will change textbook knowledge. He thanks all participating scientists from the RVZ and the University Hospital Würzburg (UKW), who were supported by colleagues from Mainz, Maastricht, and the USA. Antibodies against GPV offer great clinical potential in the treatment of disturbed hemostasis In another approach, the research group generated antibodies against GPV that prevent thrombin-mediated cleavage of GPV. "In our studies, we were able to show that these antibodies increase thrombin activity, resulting in increased fibrin formation. Our idea was therefore to use these antibodies in the context of impaired hemostasis to increase fibrin formation," says Professor David Stegner, head of the Vascular Imaging Group at RVZ and one of the study's last authors. In addition to genetic causes, a reduced platelet count or impaired function can also be caused by pharmacological treatment and therefore lead to an impaired hemostasis. Treatment with platelet aggregation inhibitors, such as clopidogrel, which are used to prevent heart attacks or strokes and to treat circulatory disorders, e.g. impairs platelet function. "In an experimental model of hemostasis, our new antibody was indeed able to restore hemostasis under conditions where hemostasis is otherwise not possible. This indicates a support of hemostasis by enhancing thrombin-dependent fibrin formation," adds Dr Sarah Beck, scientist at the Würzburg Institute for Experimental Biomedicine and first author of the study. "Anti-GPV treatment could have great clinical potential. This will be investigated in more detail in the future."