Biology subjects

Wawrzinek, R.

Publications and source records attributed to Wawrzinek, R..

3 recordsLinked to original sources

bioRxiv2025

Langerhans Cell-targeted mRNA Delivery: A Strategy for Dose-Sparing and Enhanced Anti-Tumor Immunity

Despite the success of mRNA therapeutics, challenges remain in optimizing immune responses and minimizing side effects. Cell-specific antigen delivery may help reduce required doses and improve vaccine efficacy. In this study, we report on the first targeted delivery system for mRNA to a specific subset of skin-resident antigen-presenting cells - Langerhans cells. By functionalizing lipid nanoparticles (LNPs) with a langerin-specific glycomimetic ligand, we achieve selective mRNA delivery to both murine and human primary Langerhans cells with minimal off-target uptake, at the same time resulting in significantly increased mRNA translation. This targeted mRNA delivery not only enhances antigen presentation and T cell responses but also enables dose-sparing and superior anti-tumor immunity compared to conventional immunization in a B16-OVA tumor model. Importantly, our platforms high compatibility with various lipid nanoparticle formulations offers a flexible and precise tool for skin-directed mRNA delivery.

immunology↗

bioRxiv2025

Langerhans Cell-targeted Protein Delivery Enhances Antigen-Specific Cellular Immune Response

Targeted antigen delivery to immune cells, particularly dendritic cells, has emerged as a promising strategy to enhance therapeutic efficacy of vaccines, while minimizing adverse effects associated with conventional immunization. In this study, we use our previously described small glycomimetic molecule that selectively recognizes the Langerhans cell (LC)-specific surface receptor Langerin and demonstrate specific delivery of protein antigens to these specialized dendritic cells. Our results show that Langerin-mediated antigen delivery significantly enhances the immune response in vivo, resulting in increased expansion and activation of antigen-specific T cells, compared to immunization with unmodified antigen. We demonstrate the feasibility of our LC-targeted platform for immune cell-specific immunization with protein antigen and underscore the potential of LCs as an access point for next-generation vaccines and immunotherapies.

immunology↗

bioRxiv2021

Information transfer in mammalian glycan-based communication

Glycan-binding proteins, so-called lectins, are exposed on mammalian cell surfaces and decipher the information encoded within glycans translating it into biochemical signal transduction pathways in the cell. These glycan-lectin communication pathways are complex and difficult to analyse. However, quantitative data with single cell resolution provides means to disentangle the associated signalling cascades. We chose C-Type lectin receptors (CLRs) expressed on immune cells as a model system to study their capacity to transmit information encoded in glycans of incoming particles. Lectin receptor NF{kappa}B-reporter cell lines expressing DC-SIGN, MCL, dectin-1, dectin-2, and mincle, as well as TNFR and TLR-1&2 in monocytic cell lines were characterized by comparing their efficiency to transmit glycan-encoded information. The information content was measured by following NF{kappa}B dependent GFP expression. While most receptors did transmit information to NF{kappa}B efficiently, we found dectin-2 to be an inefficient signalling receptor. Yet upon closer analysis we show that the sensitivity of the dectin-2 signal transduction pathway (EC50) can be enhanced by overexpression of its co-receptor FcR{gamma}, while its transmitted information cannot. In this context, we expanded our investigation towards the integration of multiple signal transduction pathways, which is crucial during pathogen recognition. We show how lectin receptors using a similar signal transduction pathway (dectin-1 and dectin-2) are being integrated; by striking a compromise between the lectins. By using dectin-2 and other lectins as example we demonstrate how cellular heterogeneity and the receptor itself determine the efficiency and therefore outcome of the signal transduction pathways.

cell biology↗