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Introduction: Primary human blood cells represent an essential model system to study physiology and disease. However, human blood is a limited resource. During healthy donor plateletpheresis, the leukoreduction system chamber (LRSC) reduces the leukocyte amount within the subsequent platelet concentrate through saturated, fluidized, particle bed filtration technology. Normally, the LRSC is discarded after apheresis is completed. Compared to peripheral blood, LRSC yields 10-fold mononuclear cell concentration. Methods: To explore if those retained leukocytes are attractive for research purposes, we isolated CD3+ T cells from the usually discarded LRSCs via density gradient centrifugation in order to manufacture CD19-targeted chimeric antigen receptor (CAR) T cells. Results: Immunophenotypic characterization revealed viable and normal CD4+ and CD8+ T-cell populations within LRSC, with low CD19+ B cell counts. Magnetic-activated cell sorting (MACS) purified CD3+ T cells were transduced with CD19 CAR-encoding lentiviral self-inactivating vectors using concentrated viral supernatants. Robust CD19 CAR cell surface expression on transduced T cells was confirmed by flow cytometry. CD19 CAR T cells were further enriched through anti-CAR MACS, yielding 80% CAR+ T-cell populations. In vitro CAR T cell expansion to clinically relevant numbers was achieved. To prove functionality, CAR T cells were co-incubated with the human CD19+ B cell precursor leukemia cell line Nalm6. Compared to unmodified T cells, CD19 CAR T cells effectively eradicated Nalm6 cells. Conclusion: Taken together, we can show that lymphocytes isolated from LRSCs of plateletpheresis sets can be efficiently used for the generation of functional CAR T cells for experimental purposes. [ABSTRACT FROM AUTHOR]

Background and Objectives: A sufficient supply of safe, high-quality blood components for transfusion is essential to the healthcare system in Germany. The requirements for the current reporting system are laid down in the German Transfusion Act. The present work elaborates on the advantages and limitations of the current reporting system and investigates the feasibility of a pilot project that collects specific data on blood supply based on weekly reports. Materials and Methods: Selected data on blood collection and supply from 2009 to 2021 derived from the §21 German Transfusion Act database were examined. In addition, a pilot study over a period of 12 months was conducted on a voluntary basis. The number of red blood cell (RBC) concentrates was documented and stock availability was calculated weekly. Results: From 2009 to 2021, the annual number of RBC concentrates decreased from 4.68 to 3.43 million, the per capita distribution decreased from 58 to 41 RBC concentrates per 1,000 inhabitants. These figures did not change significantly during the COVID-19 pandemic. The data of the 1-year pilot project represented 77% of the released RBC concentrates in Germany. Percentage share of O RhD positive RBC concentrates fluctuated between 35% and 22% and for O RhD negative concentrates between 17% and 5%. The availability of O RhD positive RBC concentrate stocks varied between 2.1 and 7.6 days. Conclusion: The data presented shows a decrease in annual RBC concentrate sales over an 11-year period and no further change over the past 2 years. A weekly monitoring of blood components detects acute problems in RBC provision and supply. Close monitoring seems helpful but should be combined with a nationwide supply strategy. [ABSTRACT FROM AUTHOR]

The pandemic spread of an infectious disease poses a plethora of challenges to society, clinicians, health care providers and regulating authorities. In order to mount a rapid response and to provide hope in a potentially catastrophic situation as the current COVID-19 pandemic, emergency plans, regulations and funding strategies have to be developed on regional, national and international levels. The speed needed to establish rapid response programs is challenged by the dynamics of the spread of the disease, the concurrent and competing development of different and potentially more effective treatment options, and not the least by regulatory uncertainty. Convalescent plasma, that is plasma collected from patients who have recovered from COVID-19 infections, has emerged as one of the first potential treatment options in the absence of drugs or vaccines with proven efficacy against SARS-CoV-2. The societal aspects of convalescent plasma and the public awareness gave an additional boost to the rapid employment of convalescent plasma donation platforms immediately after the SARS-CoV-2 outbreak. At the same time, uncertainty remains as to the efficacy of convalescent plasma. With evidence mostly limited to empirical reports, convalescent plasma has been used for decades for the prophylaxis and treatment of various infectious diseases. Clinical trials have addressed different infectious agents, stages of disease, target groups of patients and yielded sometimes inconclusive results. The aim of this short review is to delineate the regulatory background for the emergency use of convalescent plasma in the USA, in the European Union and in Germany, and the transition to the setting of clinical trials. In addition, we describe observations made in the process of collecting COVID-19 convalescent plasma (herein referred to as CCP), and formulate proposals to further improve the framework for rapid responses in future emergency situations. [ABSTRACT FROM AUTHOR]

Since almost 30 years, lung transplantation is a considerable therapeutic option in patients suffering from end-stage lung disease. Up to now, the impact of donor-specific antibodies directed against donor HLA (human leukocyte antigen) before and after transplantation is still a matter of debate. As histocompatibility testing is not required for each patient according to the current national guidelines and Eurotransplant recommendations for lung transplantation, each transplantation unit has to establish a local protocol together with the tissue typing laboratory how to implement an immunological risk assessment strategy for their patients while enabling access to transplantation. Desensitization regimens might help in case of highly alloimmunized patients waiting for urgent transplantation. [ABSTRACT FROM AUTHOR]

For years, cancer treatment was dominated by chemotherapy, radiation therapy, and stem cell transplantation. New insights into genetic characteristics of leukemic cells have initiated the development of the chimeric antigen receptor (CAR) T-cell therapy. This type of adoptive cell immunotherapy has been a breakthrough in the treatment of aggressive B-cell lymphoma and B-cell precursor acute lymphoblastic leukemia. In August 2018, the European Commission has approved the first CAR T-cell products – tisagenlecleucel (Kymriah®, Novartis) and axicabtagene ciloleucel (Yescarta®, Gilead) – for hematological neoplasms in Europe. As CAR T cells are a living drug, its benefits can last for many years. The administration of CAR T cells is a complex and costly endeavor involving cell manufacture, shipping of apheresis products, and management of novel and severe adverse reactions. The most common toxicities observed after CAR T-cell therapy are cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Current research focuses on improved safety and efficacy in hematological malignancies as well as the translation of CAR T-cell therapy to solid tumors. This review covers the development and current status of CAR T-cell therapy in a clinical setting with focus on challenges and future opportunities. [ABSTRACT FROM AUTHOR]

Once a cohort exceeds a certain size, it becomes mandatory to assign an identifier (ID) for each individual to ensure a secure, reliable, and unambiguous assignment. In the field of hematopoietic stem cell transplantation, with a still growing number of voluntary unrelated donors, it was recognized that a system needs to be developed to uniquely identify potential donors on a global scale to facilitate communication and to prevent errors in identification of donors. Efforts in this respect resulted in establishment of the GRID, with a defined structure and allocated rules. To successfully implement such a project, collaboration among all organizations involved in the process of volunteer donor recruitment, facilitation, and provision of hematopoietic stem cell products is necessary. Therefore, rapidly accessible information combined with a high level of communication and exchange of experiences is crucial. Established systems like the ISBT 128 and the Single European Code (SEC), which standardize the terminology, identification, coding, and labeling of tissues and cells of human origin, serve as a basis on how to successfully implement the GRID on a global scale. [ABSTRACT FROM AUTHOR]

The article reports that Advanced therapy medicinal products (ATMPs) are medicines for human use that are based on genes, tissues, or cells. They are classified into three main types: gene therapy medicines (GTP, P stands for "Product"), somatic-cell therapy medicines, and tissue-engineered medicines. Currently, the Committee for Advanced Therapies of the European Medicines Agency (.

The article offers information on the applications of immunotherapy in hematology and oncology. Topics discussed include clinical effectiveness of transplantation of autologous and allogeneic hematopoietic stem and progenitor cells after conditioning therapies; advancements in the fields of mesenchymal stromal cells (MSC) and autologous chimeric antigen receptor T cells (CAR-T cells) therapies; and a discussion on clinical application, potential problems and future developments in this field.

Background: In patients failing successful conventional mobilization of hematopoietic progenitor cells (HPC) plerixafor (Mozobil®) seems to be an alternative. We report a series of 14 patients with multiple myeloma or NHL successfully mobilized and harvested by plerixafor together with large-volume leukaphereses (LVL). Methods: In a first series (GI), 5 patients were mobilized with G-CSF and plerixafor. In the second series (GII), 9 patients were mobilized by chemotherapy, G-CSF, and plerixafor. Results: In GI and GII, addition of plerixafor led to a significant (p < 0.01) increase of leukocytes and CD34+ cells in peripheral blood (PB). In GII, the median number of CD34+ cells in PB before and after addition of plerixafor was significantly (p = 0.019) higher compared to GI (9 vs. 5 and 50 vs. 24 cells/µl, respectively). In GI and GII, a median number of three or one aphereses was performed. In GII, the median yield (6.7 × 106 CD34+ cells/kg) of the first apheresis and the median intra-apheresis recruitment of CD34+ cells were significantly (p < 0.05) higher compared to GI (2.94 × 106 CD34+ cells/kg). All patients transplanted, 5 in GI and 8 in GII, exhibited successful engraftment. Conclusions: Plerixafor and G-CSF mobilization or the addition of plerixafor during non-optimal chemotherapy and G-CSF mobilization together with LVL enabled, independent of leukocyte count and even without detectable CD34+ cells before addition of plerixafor, sufficient harvest of HPC numbers for transplantation. Addition of plerixafor during chemotherapy and G-CSF mobilization led to an increased intra-apheresis recruitment and a significantly higher yield of CD34+ cells compared to plerixafor and G-CSF steady-state mobilized patients. © 2013 S. Karger GmbH, Freiburg [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editors discuss topics within the issue related to existing and new antibody engineering technologies, including phage display, the therapeutic potential of alternative human isotypes and Fc engineering strategies.

No abstract available [ABSTRACT FROM AUTHOR]