Philipp D. Kaiser

Longitudinal analysis of humoral and cellular immunity in SARS-CoV-2 exposed families

Alex Dulovic, Armin Rabsteyn, Jonathan Remppis, Irene K. E. Gentzcke et autres

Identification of previous SARS-CoV-2 infection typically relies on serology, yet T-cells play a key role in the adaptive immune response against SARS-CoV-2. Here, we investigated in parallel the SARS-CoV-2-specific as well as endemic human coronavirus-specific humoral and cross-reactive cellular responses in children …

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PET-based immunomapping of intratumoral CD4+ cells to monitor acquired resistance to checkpoint inhibitors

Stefania Pezzana, Simone Blaess, Bjoern Traenkle, Anna Schaefer et autres

CD4+ T cells are crucial in shaping response and resistance to immunotherapy. To enhance our understanding of their multifaceted functions, we developed copper-64-radiolabeled nanobodies targeting the human CD4 receptor (64Cu-CD4-Nb1) for positron emission tomography (PET). In human CD4-receptor knock-in mice, 64Cu-CD4-Nb1 specifically …

PET-based immunomapping of intratumoral CD4 + cells to monitor acquired resistance to checkpoint inhibitors

Stefania Pezzana, Simone Blaess, Bjoern Traenkle, Lara Ruoff et autres

CD4 + T cells are crucial in shaping response and resistance to immunotherapy. To enhance our understanding of their multifaceted functions, we developed copper-64–radiolabeled nanobodies targeting the human CD4 receptor ( 64 Cu-CD4-Nb1) for positron emission tomography (PET). In human CD4-receptor knock-in …

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PET-based immunomapping of intratumoral CD4+ cells to monitor acquired resistance to checkpoint inhibitors

Stefania Pezzana, Simone Blaess, Anna Schaefer, Lara Ruoff et autres

ECM Proteins Nidogen‐1 and Decorin Restore Functionality of Human Islets of Langerhans upon Hypoxic Conditions

Abiramy Jeyagaran, Max Urbanczyk, Daniel Carvajal Berrio, Teresa Baldissera et autres

Transplantation of donor islets of Langerhans is a potential therapeutic approach for patients with diabetes mellitus; however, its success is limited by islet death and dysfunction during the initial hypoxic conditions at the transplantation site. This highlights the need to support the …

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Development of a PNGase Rc column for online deglycosylation of complex glycoproteins during HDX-MS

Thomas Lambert, Marius Gramlich, Luisa S. Stutzke, Luke Smith et autres

ABSTRACT Protein glycosylation is one of the most common PTMs and many cell surface receptors, extracellular proteins and biopharmaceuticals are glycosylated. However, HDX-MS analysis of such important glycoproteins has so far been limited by difficulties in determining the HDX of the protein …

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Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells

Teresa R. Wagner, Simone Blaess, Inga B. Leske, Desiree Isabella Frecot et autres

Abstract Signal-regulatory protein α (SIRPα) expressed by myeloid cells is of particular interest for therapeutic strategies targeting the interaction between SIRPα and the "don’t eat me" ligand CD47 and as a marker to monitor macrophage infiltration into tumor lesions. To address both …

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A novel PNGase Rc for improved protein N-deglycosylation in bioanalytics and HDX-MS epitope mapping under challenging conditions

Marius Gramlich, Sandra M. Maier, Philipp D. Kaiser, Bjoern Traenkle et autres

Abstract N-linked glycosylation is a ubiquitous posttranslational modification of proteins. While it plays an important role in the biological function of proteins, it often poses a major challenge for their analytical characterization. Currently available peptide N-glycanases (PNGases) are often inefficient at deglycosylating …

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Decisive role of water and protein dynamics in residence time of p38α MAP kinase inhibitors

Tatu Pantsar, Philipp D. Kaiser, Mark Kudolo, Michael Förster et autres

Abstract Target residence time plays a crucial role in the pharmacological activity of small molecule inhibitors. Little is known, however, about the underlying causes of inhibitor residence time at the molecular level, which complicates drug optimization processes. Here, we employ all-atom molecular …

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Improved targeting of human CD4+ T cells by nanobody-modified AAV2 gene therapy vectors

Martin V. Hamann, Niklas Beschorner, Xuan‐Khang Vu, Ilona Hauber et autres

Adeno-associated viruses (AAV) are considered non-pathogenic in humans, and thus have been developed into powerful vector platforms for in vivo gene therapy. Although the various AAV serotypes display broad tropism, frequently infecting multiple tissues and cell types, vectors for specific and efficient …

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