Dirk H. Busch
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View article: Tissue-adapted Tregs harness inflammatory signals to promote intestinal repair from therapy-related injury
Tissue-adapted Tregs harness inflammatory signals to promote intestinal repair from therapy-related injury Open
Intestinal stem cells (ISCs) promote tissue repair after genotoxic or immune-mediated injury. However, ISCs are particularly sensitive to various stressors and primary targets of overwhelming immune responses, such as interferon γ (IFNγ)-m…
View article: Epigenetically Controlled <i>ZEB2</i> Expression Promotes the Cytotoxic Potential of CMV‐Specific CD8 <sup>+</sup> T Cells
Epigenetically Controlled <i>ZEB2</i> Expression Promotes the Cytotoxic Potential of CMV‐Specific CD8 <sup>+</sup> T Cells Open
Zinc finger E‐box binding protein 2 (ZEB2) is a key factor in the differentiation of naïve CD8 + T cells into effector and memory T cells. However, the precise regulatory role of ZEB2 in cytotoxic CD8 + T cells remains unknown. Our recent …
View article: TCR activation impairs CAR-T cytotoxicity against separate target cells
TCR activation impairs CAR-T cytotoxicity against separate target cells Open
Chimeric antigen receptor T cells (CAR-T) are effective therapeutics against cancer and autoimmunity, but whether the endogenous T cell receptor (TCR) is beneficial, detrimental or irrelevant for CAR T function and patient outcome remains …
View article: Guiding Antiviral Cell Therapy Approaches with an Online Resource of Clinically Scored Epitopes, T-Cell Receptors, and B-Cell Receptors
Guiding Antiviral Cell Therapy Approaches with an Online Resource of Clinically Scored Epitopes, T-Cell Receptors, and B-Cell Receptors Open
Introduction: The clinical application of cell-based immunotherapies is a rapidly emerging field, and recent advances in gene therapy have opened up a new era of innovative treatment approaches. Introducing a specific T-cell receptor (TCR)…
View article: Call for preserving specialized knowledge and contributions of the CAT to advancing ATMPs in Europe
Call for preserving specialized knowledge and contributions of the CAT to advancing ATMPs in Europe Open
With the proposal for major reform of the pharmaceutical legislation (Regulation (EU) 2023/0131, Directive (EU) 2023/0132) in April 2023, the foundations of Europe's regulatory architecture are being reshaped. The revised legislation propo…
View article: Treatment-dependent T-cell infiltrate in pediatric eosinophilic esophagitis (EoE)
Treatment-dependent T-cell infiltrate in pediatric eosinophilic esophagitis (EoE) Open
View article: The V5-Epitope Tag for Cell Engineering and Its Use in Immunohistochemistry and Quantitative Flow Cytometry
The V5-Epitope Tag for Cell Engineering and Its Use in Immunohistochemistry and Quantitative Flow Cytometry Open
Synthetic biology has fundamentally advanced cell engineering and helped to develop effective therapeutics such as chimeric antigen receptor (CAR)-T cells. For these applications, the detection, localization, and quantification of heterolo…
View article: Risk factors for vancomycin resistance in patients with <i>Enterococcus faecium</i> bloodstream infections: an analysis of the Munich Multicentric Enterococci Cohort
Risk factors for vancomycin resistance in patients with <i>Enterococcus faecium</i> bloodstream infections: an analysis of the Munich Multicentric Enterococci Cohort Open
Enterococcus faecium is difficult to treat owing to its intrinsic and acquired resistance to antibiotics, particularly vancomycin. Vancomycin-resistant Enterococcus faecium is an important cause of bloodstream infections in healthcare sett…
View article: Optimizing CD34+ cell doses for large-scale translational, single donor humanized mouse experiments
Optimizing CD34+ cell doses for large-scale translational, single donor humanized mouse experiments Open
Humanized mice are a powerful tool in preclinical assessment of novel therapeutics. However, generation of large homogenous cohorts is believed to be hampered by the limited number of human stem cells retrievable from individual donors, li…
View article: A distinct priming phase regulates CD8 T cell immunity by orchestrating paracrine IL-2 signals
A distinct priming phase regulates CD8 T cell immunity by orchestrating paracrine IL-2 signals Open
T cell priming is characterized by an initial activation phase that involves stable interactions with dendritic cells (DCs). How activated T cells receive the paracrine signals required for their differentiation once they have disengaged f…
View article: High-resolution profile of neoantigen-specific TCR activation links moderate stimulation to increased resilience of engineered TCR-T cells
High-resolution profile of neoantigen-specific TCR activation links moderate stimulation to increased resilience of engineered TCR-T cells Open
View article: Susceptibility to inflammatory bowel diseases promotes invasive carcinomas in a murine model of ATF6-driven colon cancer
Susceptibility to inflammatory bowel diseases promotes invasive carcinomas in a murine model of ATF6-driven colon cancer Open
Chronic inflammation in inflammatory bowel disease (IBD) patients represents a risk factor for developing colitis-associated cancer (CAC). We previously linked the endoplasmic reticulum unfolded protein response (UPRER) signal transducer a…
View article: Engineering de novo binder CAR-T cell therapies with generative AI
Engineering de novo binder CAR-T cell therapies with generative AI Open
Chimeric antigen receptor T cell (CAR-T) therapies have revolutionized cancer treatment, with six CAR-T products currently in clinical use 1–4 . Despite their success, high resistance rates due to antigen escape remain a major challenge 5,…
View article: Quality of vaccination-induced T cell responses is conveyed by polyclonality and high, but not maximum, antigen receptor avidity
Quality of vaccination-induced T cell responses is conveyed by polyclonality and high, but not maximum, antigen receptor avidity Open
While the quantity of vaccination-induced T cells represents a routine immunogenicity parameter, the quality of such responses is poorly understood. We here report on a clinical cohort of 29 human healthy individuals who received three mRN…
View article: TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation
TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation Open
Low antigen sensitivity and a gradual loss of effector functions limit the clinical applicability of chimeric antigen receptor (CAR)–modified T cells and call for alternative antigen receptor designs for effective T cell–based cancer immun…
View article: Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases
Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases Open
Pro-inflammatory autoantigen-specific CD4+ T helper (auto-Th) cells are central orchestrators of autoimmune diseases (AIDs). We aimed to characterize these cells in human AIDs with defined autoantigens by combining human leukocy…
View article: Deconstructing CTL-mediated autoimmunity through weak TCR-cross-reactivity towards highly abundant self-antigen
Deconstructing CTL-mediated autoimmunity through weak TCR-cross-reactivity towards highly abundant self-antigen Open
T-cell antigen receptors (TCRs) exhibit inherent cross-reactivity which broadens the spectrum of epitopes that are recognizable by a finite TCR-repertoire but also carries the risk of autoimmunity. However, TCRs support also a high level o…
View article: Metabolization of microbial postbiotic pentanoate drives anti-cancer CAR T cells
Metabolization of microbial postbiotic pentanoate drives anti-cancer CAR T cells Open
The microbiome is a complex host factor and key determinant of the outcome of antibody-based and cellular immunotherapy. Its postbiotics are a blend of soluble commensal byproducts that are released into the host environment and have been …
View article: Predicting T cell receptor functionality against mutant epitopes
Predicting T cell receptor functionality against mutant epitopes Open
View article: Automatisierte Surveillance und Risikovorhersage mit dem Ziel einer risikostratifizierten Infektionskontrolle und -prävention (RISK Prediction for Risk-stratified Infection Control and Prevention)
Automatisierte Surveillance und Risikovorhersage mit dem Ziel einer risikostratifizierten Infektionskontrolle und -prävention (RISK Prediction for Risk-stratified Infection Control and Prevention) Open
View article: Erratum for Rothe et al., “Are enterococcal bloodstream infections an independent risk factor for a poorer 5-year survival or just a marker for severity of illness?—The Munich multicentric enterococci cohort”
Erratum for Rothe et al., “Are enterococcal bloodstream infections an independent risk factor for a poorer 5-year survival or just a marker for severity of illness?—The Munich multicentric enterococci cohort” Open
View article: PGE2 limits effector expansion of tumour-infiltrating stem-like CD8+ T cells
PGE2 limits effector expansion of tumour-infiltrating stem-like CD8+ T cells Open
View article: HLA reduction of human T cells facilitates generation of immunologically multicompatible cellular products
HLA reduction of human T cells facilitates generation of immunologically multicompatible cellular products Open
Adoptive cellular therapies have shown enormous potential but are complicated by personalization. Because of HLA mismatch, rejection of transferred T cells frequently occurs, compromising the T-cell graft's functionality. This obstacle has…
View article: Discovery of a monoclonal, high-affinity CD8+ T cell clone following natural hepatitis C virus infection
Discovery of a monoclonal, high-affinity CD8+ T cell clone following natural hepatitis C virus infection Open
CD8+ T cells recognising their cognate antigen are typically recruited as a polyclonal population consisting of multiple clonotypes with varying T-cell receptor (TCR) affinity to the target peptide-MHC (pMHC) complex. Advances in single-ce…
View article: Issue Information: Eur. J. Immunol. 4'24
Issue Information: Eur. J. Immunol. 4'24 Open
View article: Viral genome sequencing to decipher in-hospital SARS-CoV-2 transmission events
Viral genome sequencing to decipher in-hospital SARS-CoV-2 transmission events Open
The SARS-CoV-2 pandemic has highlighted the need to better define in-hospital transmissions, a need that extends to all other common infectious diseases encountered in clinical settings. To evaluate how whole viral genome sequencing can co…
View article: B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4
B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4 Open
Neuromyelitis optica is a paradigmatic autoimmune disease of the central nervous system, in which the water-channel protein AQP4 is the target antigen 1 . The immunopathology in neuromyelitis optica is largely driven by autoantibodies to A…
View article: A mass cytometry approach to track the evolution of T cell responses during infection and immunotherapy by paired T cell receptor repertoire and T cell differentiation state analysis
A mass cytometry approach to track the evolution of T cell responses during infection and immunotherapy by paired T cell receptor repertoire and T cell differentiation state analysis Open
T cell receptor (TCR) recognition followed by clonal expansion is a fundamental feature of adaptive immune responses. Here, we developed a mass cytometric (CyTOF) approach combining antibodies specific for different TCR Vα– and Vβ-chains w…
View article: A chimeric antigen receptor-based cellular safeguard mechanism for selective in vivo depletion of engineered T cells
A chimeric antigen receptor-based cellular safeguard mechanism for selective in vivo depletion of engineered T cells Open
Adoptive immunotherapy based on chimeric antigen receptor (CAR)-engineered T cells has exhibited impressive clinical efficacy in treating B-cell malignancies. However, the potency of CAR-T cells carriethe potential for significant on-targe…
View article: Miniaturized CAR knocked onto CD3ε extends TCR function with CAR specificity under control of endogenous TCR signaling cascade
Miniaturized CAR knocked onto CD3ε extends TCR function with CAR specificity under control of endogenous TCR signaling cascade Open
Immunotherapy using TCR and especially CAR transgenic T cells is a rapidly advancing field with the potential to become standard of care for the treatment of multiple diseases. While all current FDA approved CAR T cell products are generat…