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The Pre-existing T Cell Landscape Determines the Response to Bispecific T Cell Engagers in Multiple Myeloma Patients
Abstract: Bispecific T cell engagers (TCEs) have shown promise in the treatment of various cancers, but the immunological mechanism and molecular determinants of primary and acquired resistance to TCEs remain poorly understood. Here, we identify conserved behaviors of bone marrow-residing T cells in multiple myeloma patients undergoing BCMAxCD3 TCE therapy. We show that the immune repertoire reacts to TCE therapy with cell state-dependent clonal expansion and find evidence supporting the coupling of tumor recognition via major histocompatibility complex class I (MHC class I), exhaustion, and clinical response. We find the abundance of exhausted-like CD8+ T cell clones to be associated with clinical response failure, and we describe loss of target epitope and MHC class I as tumor-intrinsic adaptations to TCEs. These findings advance our understanding of the in vivo mechanism of TCE treatment in humans and provide the rationale for predictive immune-monitoring and conditioning of the immune repertoire to guide future immunotherapy in hematological malignancies
Immunotherapies for Acute Myeloid Leukemia
The efficacy of immunotherapeutic approaches in the treatment of different cancer types is becoming increasingly obvious, and immunotherapies in cancer treatment have experienced a significant breakthrough in the last few years. Immunotherapy encompasses several diverse treatment approaches, each of which has a distinct mechanism of action, and all of which are designed to boost or restore immune function in some manner. Consequently, T cell activating immunotherapeutic approaches like immune checkpoint inhibition, chimeric antigen receptor T cells (CARs), or bi-specific T cell activating antibodies are becoming increasingly important treatment strategies in different solid tumor types as we...
Genomic Investigation and Successful Containment of an Intermittent Common Source Outbreak of OXA-48-producing Enterobacter Cloacae Related to Hospital Shower Drains
Abstract: The hospital environment has been reported as a source of transmission events and outbreaks of carbapenemase-producing Enterobacterales. Interconnected plumbing systems and the microbial diversity in these reservoirs pose a challenge for outbreak investigation and control. A total of 133 clinical and environmental OXA-48-producing Enterobacter cloacae isolates collected between 2015 and 2021 were characterized by whole-genome sequencing (WGS) to investigate a prolonged intermittent outbreak involving 41 patients in the hematological unit. A mock-shower experiment was performed to investigate the possible acquisition route. WGS indicated the hospital water environmental reservoir as...
Myeloische Neoplasien
Eine Übersicht der rasanten Entwicklungen im Bereich der myeloischen Erkrankungen - Dieses Buch stellt kompakt und praxisorientiert aktuelle diagnostische und therapeutische Verfahren dar und bietet so eine gute Unterstützung sowohl bei der Akutversorgung im Krankenhaus als auch bei der langfristigen Betreuung der Patienten im ambulanten Bereich. Neben pathophysiologischen und molekularen Grundlagen und der aktuellen Klassifikation werden auch zukünftige Aspekte der Diagnostik und Therapie myeloischer Neoplasien aufgezeigt.
Algorithms in Bioinformatics
This book constitutes the refereed proceedings of the 8th International Workshop on Algorithms in Bioinformatics, WABI 2008, held in Karlsruhe, Germany, in September 2008 as part of the ALGO 2008 meeting. The 32 revised full papers presented together with the abstract of a keynote talk were carefully reviewed and selected from 81 submissions. All current issues of algorithms in bioinformatics are addressed, reaching from mathematical tools to experimental studies of approximation algorithms and reports on significant computational analyses. The topics range in biological applicability from genome mapping, to sequence assembly, to microarray quality, to phylogenetic inference, to molecular modeling.
Targeted Therapies in Cancer
From its introduction, oncological chemotherapy has been encumbered by poor selectivity because antiproliferative drugs are often toxic not only to tumor cells but also to important populations of the body’s non-neoplastic cells. Modern targeted therapies interact with defined molecules present on cancer cells, adding increased selectivity to their toxic effects. This book presents an integrated critical view on the theories, mechanisms, problems and pitfalls of the targeted therapy approach.
