Publications by authors named "Marlene Biehl"

Article Synopsis
  • Multiple myeloma (MM) is still an incurable cancer despite available therapies, with T-cell bispecific antibodies (TCBs) targeting BCMA and GPRC5D showing promise but facing issues like resistance and relapse due to antigen loss.
  • Forimtamig is a novel GPRC5D-targeting TCB that works more effectively than traditional formats by forming stable immunological connections, leading to better tumor cell destruction and T cell activation in preclinical studies.
  • Current research is exploring forimtamig in clinical trials for relapsed and refractory MM patients, both alone and alongside traditional care and new therapies, to enhance treatment outcomes and prevent relapses.
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Purpose: Target-dependent TCB activity can result in the strong and systemic release of cytokines that may develop into cytokine release syndrome (CRS), highlighting the need to understand and prevent this complex clinical syndrome.

Experimental Design: We explored the cellular and molecular players involved in TCB-mediated cytokine release by single-cell RNA-sequencing of whole blood treated with CD20-TCB together with bulk RNA-sequencing of endothelial cells exposed to TCB-induced cytokine release. We used the in vitro whole blood assay and an in vivo DLBCL model in immunocompetent humanized mice to assess the effects of dexamethasone, anti-TNFα, anti-IL6R, anti-IL1R, and inflammasome inhibition, on TCB-mediated cytokine release and antitumor activity.

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Article Synopsis
  • T-cell Bispecific Antibodies (TCBs) enhance anti-tumor responses by linking T-cells to tumor cells, even in patients without antigen-specific T-cells or with non-inflamed tumors.
  • TCB treatment was shown to significantly reduce tumor growth and increase the number of tumor-infiltrating T-cells, indicating an activated immune response and the possible involvement of the CXCL10-CXCR3 pathway in T-cell recruitment.
  • Combining TCBs with anti-PD-L1 antibodies improved treatment efficacy and highlighted the PD-1/PD-L1 interaction as a resistance mechanism that can be targeted to enhance anti-tumor activity.
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Vaccine platforms that can be flexibly loaded with antigens can contribute to decrease response time to emerging infections. For many pathogens and chronic infections, induction of a robust cytotoxic T lymphocytes-mediated response is desirable to control infection. Antigen delivery into the cytoplasm of antigen presenting cells favors induction of cytotoxic T cells.

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Donor CD4(+)Foxp3(+) regulatory T cells (T reg cells) suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HCT [allo-HCT]). Current clinical study protocols rely on the ex vivo expansion of donor T reg cells and their infusion in high numbers. In this study, we present a novel strategy for inhibiting GvHD that is based on the in vivo expansion of recipient T reg cells before allo-HCT, exploiting the crucial role of tumor necrosis factor receptor 2 (TNFR2) in T reg cell biology.

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Inhibition of the tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) system reduces intestinal cell death and disease development in several models of colitis. In view of the crucial role of TNF and intestinal cell death in graft-versus-host disease (GVHD) and the ability of TWEAK to enhance TNF-induced cell death, we tested here the therapeutic potential of Fn14 blockade on allogeneic hematopoietic cell transplantation (allo-HCT)-induced intestinal GVHD. An Fn14-specific blocking human immunoglobulin G1 antibody variant with compromised antibody-dependent cellular cytotoxicity (ADCC) activity strongly inhibited the severity of murine allo-HCT-induced GVHD.

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The cytokine tumor necrosis factor (TNF) has pleiotropic functions both in normal physiology and disease. TNF signals by the virtue of two cell surface receptors, TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). Exogenous TNF promotes experimental metastasis in some models, yet the underlying mechanisms are poorly understood.

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This study explores the impact of Hsp90 inhibitors NVP-AUY922 and NVP-BEP800 in combination with ionizing radiation (IR) on the migration and invasion of lung carcinoma A549 and glioblastoma SNB19 cells, under normoxia or hypoxia. Independent of oxygen concentration, both drugs decreased the migration and invasion rates of non-irradiated tumor cells. Combined drug-IR treatment under hypoxia inhibited cell invasion to a greater extent than did each treatment alone.

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