Biology subjects

Retiere, C.

Publications and source records attributed to Retiere, C..

3 recordsLinked to original sources

bioRxiv2025

Ultrafast tyrosine-based cell membrane modification via diazonium salts: a new frontier for biomedical applications

In this study, we present an ultrafast, efficient, and broadly applicable strategy for cell membrane modification via tyrosine bioconjugation using diazonium salt derivatives. This chemical approach enables both one-step and two-step functionalization of adherent, suspension, and primary cells with diverse ligands, including imaging probes, carbohydrates, biotin, and proteins, without inducing cytotoxicity or immune activation. Membrane engineering through bioconjugation is emerging as a valuable tool in biomedical research, given the cell membranes central role in signaling, transport, and cell-cell interactions. Compared to traditional glyco-engineering methods that often require multiday incubations and can cause cellular stress, our approach achieves precise and high-density grafting in less than one hour, with improved reproducibility and biological compatibility. Importantly, we demonstrate that this strategy can be applied to a variety of cell types, encompassing both immortalized cell lines and primary cells, notably Peripheral Blood Mononuclear Cells (PBMCs) and human effector cells such as natural killer (NK) cells, to enhance their cytotoxic function against EGFR-positive cancer cells via surface-conjugated Nanofitin. Moreover, we show that the bioconjugated signal diminishes over time due to cell division, offering a self-limiting alternative to permanent genetic modifications such as CAR-T, thereby mitigating risks associated with overly prolonged immune activation. Finally, the feasibility of storing pre-functionalized cells at -80 {degrees}C expands the practicality of this platform for future ready-to-use applications. Together, these features make our method a compelling alternative to current technologies for applications in targeted therapy, diagnostics, and cell-based immunotherapy.

bioengineering↗

bioRxiv2020

A DNA vaccine strategy to activate natural killer cells for therapeutic targeting of XPO1-positive tumors

Natural killer (NK) cells are key components of the immune response to viral infections and cancer. Their functions are controlled by activating and inhibitory killer-cell immunoglobulin-like receptors (KIR) which have MHC class I ligands. KIR2DS2 is an activating KIR, that binds conserved viral peptides in the context of HLA-C and has been associated with protective responses to both cancer and viral infections. We sought to investigate whether NK cells can be specifically activated in a peptide:MHC dependent manner to generate functional immune responses as a potential immunotherapeutic strategy. We developed a peptide-based KIR targeting DNA vaccine. Immunizing KIR-Tg mice with the vaccine construct generated in vivo peptide-specific activation of KIR2DS2-positive NK cells leading to canonical and cross-reactive peptide specific immune responses in vitro, and also in vivo inhibition of tumor growth. Using immunopeptidomics we identified that the nuclear export protein XPO1, which has been associated with a poor prognosis in many different human cancers, furnishes an HLA-C restricted cancer-associated peptide ligand for KIR2DS2-positive NK cells. We thus define a novel strategy to activate KIR in a peptide-specific manner and identify a rationale for its use in cancer immunotherapy. Significance statementNatural killer (NK) cells are known to have important roles in determining the outcomes of viral infections and cancer. The killer cell immunoglobulin-like receptors (KIR), and in particular the activating receptor KIR2DS2, have been associated with the outcome of a number of different human cancers. Specific activation of NK cells through KIR2DS2 is challenging because it shares high (>98%) sequence homology with related inhibitory KIR. We have used a peptide:MHC targeting strategy to activate NK cells through KIR2DS2 and identified a novel cancer-associated ligand for this receptor. The work provides a proof-of-concept for targeting NK cells through activating KIR as a cancer immunotherapy strategy.

immunology↗

bioRxiv2018

High-resolution genetic and phenotypic analysis of KIR2DL1 alleles and their association with pre-eclampsia

Killer-cell immunoglobulin-like receptor (KIR) genes are inherited as haplotypes, expressed by NK cells and linked to outcomes of infectious diseases and pregnancy. Understanding how genotype relates to phenotype is difficult because of the extensive diversity of the KIR family. Indeed, high-resolution KIR genotyping and phenotyping in single NK cells in the context of disease association is lacking. Here, we describe a new method to separate NK cells expressing allotypes of the KIR2DL1 gene carried by the KIR A haplotype (KIR2DL1A) from those expressing KIR2DL1 alleles carried by the KIR B haplotype (KIR2DL1B). We find that in KIR AB heterozygous individuals, different KIR2DL1 allotypes can be detected both in peripheral blood and in uterine single NK cells. Using this new method, we demonstrate that both blood and uterine NK cells co-dominantly express KIR2DL1A and KIR2DL1B allotypes, but with a predominance of KIR2DL1A variants, which associate with enhanced NK cell function. In a case-control study of pre-eclampsia, we show that KIR2DL1A, not KIR2DL1B, associates with increased disease risk. This method will facilitate our understanding of how individual KIR2DL1 allelic variants affect NK cell function and contribute to disease risk.

immunology↗