Medical University of Warsaw

EOG21 Theranostic Exosomes in Personalized Cancer Nanomedicine -Cancer is currently second cause of death behind cardiovascular diseases in the European Union. Among different cancers, lung cancer is the most common cause of global cancer-related mortality due to late diagnoses and limited treatment, leading to over a million deaths each year. Accumulating evidence suggests that lung cancer represents a group of histologically and molecularly heterogeneous diseases. Recent strategies, e.g., surgery, radiotherapy, chemo- and immunotherapy, to treat lung cancer are still far to be sufficient for suffering patients. The application of nanotechnology to treat lung cancer unleashes a huge capacity to solve many unmet lung cancer clinical needs and the potential for development in the coming future. Our proposal consists of an ambitious and responsible transnational research and development program of cancer theranostics using nanotechnology for personalised nanomedicine. The proposal integrates nanoscience products and their technological applications resulting in completely new ideas, methods and outputs, based on the bioengineering of a highly sensitive and highly reliable multifunctional self-navigated MRI-guided and thermallyrearranged patient-personalized "Theranostic Exosome Drug Delivery System" (TEDDS). This system can deliver and monitor using MRI, an enzyme-based sensing program by a "Trojan horse"-like effect, employing radiotherapy combined with magnetic fluid hyperthermia treatments. The TEDDS drug candidate will be tested in preclinical safety programs addressing common regulatory issues and using novel approaches such as 3D cultures, organ-on-a-chip, microfluidics and proteomic profiling. To reach these challenges, the project will merge multinational teams representing Polish and Norwegian laboratories, academia, clinical hospital, and industrial partnerships to elucidate different areas of biosciences, nanotechnology, clinical oncology and pharmaceutical business ventures.

ABM11 Assessment of the incidence of persistent pulmonary hypertension of the newborn in a group of newborns born between 32 and 42 weeks of gestation treated with salbutamol -The primary objective of the clinical trial will be to assess the incidence of PPHN (PPHN-persistent pulmonary hypertension of the newborn) defined as the need for ventilation with FiO2 > 0.50 and echocardiographic signs of increased pulmonary pressure (left-right or bidirectional shunt through a patent ductus arteriosus) or the need for ventilation with FiO2 > 0.50 and a difference in pre- and post-ductal saturation > 20%) in the treatment of respiratory failure in a group of newborns born between 32 and 41 weeks of gestation. The secondary objectives will be to assess the modified Silverman scale, hereinafter referred to as the "TTN scale" in comparison to the concentration of oxygen used during ventilation and the intervention used, and to assess the parameters of the acid-base balance test: pH, carbon dioxide tension (pCO2), base deficiency (BE) in the compared groups. The study was planned as a prospective, multicenter, double-blind, randomized, placebo-controlled study.

EOG22 The goal of the ALTERCAR project is to develop novel, alternative, chimeric antigen receptor (CAR)-based therapeutic solutions for leukemia and lymphoma patients with poor prognosis. The collaboration within the Consortium provides a unique opportunity to implement CAR-T cell technology in Poland and develop alternative CAR-T cells with new specificities, which may constitute a significant advancement in CAR therapy. The long-term outcome of the project will be the establishment of a sustainable Polish-Norwegian network for the development, production and preparation of CAR-based and other adoptive therapies for clinical studies in various forms of cancer. In the first stage of the project, we employ a combined bioinformaticstranscriptomicprote... approach to select new targets for CAR-T cell immunotherapy using established tumor cell lines. Chosen antigens were extensively validated in primary cells isolated from acute lymphoblastic leukemia and lymphoma patients refractory to standard-of-care treatment. As a result of the first step we select 2-4 antigens as candidates for CAR therapy, which in the second stage of the project will be used for designing a panel of CAR constructs. The initially designed construct will be affinity-optimized and in a subsequent stage of the project validated in pre-clinical settings using well-established in vitro and in vivo models. In the final stage, selected CAR candidate/s will be manufactured as GMP-grade RNA for the first-in-man study. The final product of this proposal will be one or more alternative CARs to be used in the treatment of patients with B cell malignancies refractory to all treatment options or patients who relapse after previous therapies.

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