bims-hummad 2026-09-27 papers

Vaccines (Basel). 2026 Sep 13. pii: 805. [Epub ahead of print]14(9):

Stepwise Evolution of Immunodeficient Mouse Models: Focus on NCG Strains and Their Applications in Humanized Immune System Research.

Hongyan Sun, Jialu Fan, Yujing Zhang, Jun Xing, Yinlian Zhang, Cunxiang Ju, Juan Liang.

Immunodeficient and humanized mouse models have become essential tools for investigating human immunity, disease pathogenesis, and therapeutic evaluation. This review summarizes the stepwise evolution of these platforms, from nude and SCID mice to advanced NOD/SCID/Il2rgnull strains (NCG, NSG, or NOG), and highlights how progressive removal of murine immune barriers has improved human cell engraftment and experimental utility. Major humanized immune system (HIS) approaches, including Hu-PBMC/PBL, Hu-HSC, and Hu-BLT models, are compared with respect to engraftment kinetics, immune composition, graft-versus-host disease, and suitability for distinct research applications. Particular emphasis is placed on next-generation engineered strains that enhance specific human immune compartments, including cytokine-humanized models for myeloid, dendritic cell, natural killer cell, and neutrophil reconstitution; TSLP-based models that restore secondary lymphoid organogenesis and improve adaptive immune responses; and advanced HLA-humanized models. These advances have substantially expanded the value of humanized mice in studies of autoimmune disease, cancer immunotherapy, and vaccine evaluation. Nevertheless, no single model fully reproduces the complexity of the human immune system, and major limitations remain, including incomplete stromal humanization, restricted HLA diversity, and inter-model variability. Continued refinement will be critical for improving translational relevance and predictive power in vaccine and immunology research.

Keywords: NCG; humanized mouse models; immune system reconstruction; immunotherapy evaluation

DOI: https://doi.org/10.3390/vaccines14090805

Diabetes Obes Metab. 2026 Sep 20.

A DPP6-Targeted PET Tracer for Non-Invasive Imaging of Transplanted Human Islets.

Amina Khalil, Arturo Roca-Rivada, Svitlana Vasylovska, Lorenzo J I Balestri, Irina Velikyan, Sayro Jawurek, Alexandra C Title, Burcak Yesildag, Luke R Odell, Joey Lau, Decio L Eizirik, Olof Eriksson.

INTRODUCTION: Dipeptidyl peptidase-like protein 6 (DPP6) is a potential molecular imaging biomarker for pancreatic and transplanted islets of Langerhans. 4hD29 is a single-domain antibody with nanomolar affinity for DPP6. Here, we demonstrate the generation and validation of [68Ga]Ga-NOTA-4hD29 for Positron Emission Tomography (PET) imaging of human stem cell-derived islets (SC-islets) and human islets.
METHODS: The binding of fluorescently labelled 4hD29 to human islets, human beta cell models and pancreatic tissues from various species over time was characterised. NOTA-4hD29 was radiolabelled with Gallium-68, and the resulting tracer [68Ga]Ga-NOTA-4hD29 was evaluated for in vitro DPP6 binding as well as in vivo biodistribution. In vivo PET imaging was performed in immunodeficient mice transplanted with 400 to 800 SC-islets or human islets, and the uptake signal was compared to non-transplanted control mice.
RESULTS: Fluorescently labelled 4hD29 demonstrated specific binding and internalisation in human islets. Fluorescence signal remained detectable for up to 2 h following incubation, indicating sustained intracellular retention. [68Ga]Ga-NOTA-4hD29 bound to human islets with high specificity, and binding intensity correlated to islet purity. The binding of fluorescent and radiolabelled 4hD29 was negligible in extra-pancreatic tissues. In vivo PET imaging enabled reliable detection of grafts comprised of 400 to 800 SC-islets or human islets in immunodeficient mice.
CONCLUSION: [68Ga]Ga-NOTA-4hD29 is a promising PET tracer for in vivo imaging of DPP6 in human islets. The tracer enabled non-invasive detection of transplanted human islet grafts in the 400-800 IEQ range and demonstrated favourable biodistribution and dosimetry profiles, supporting its further development for islet imaging applications.

Keywords: DPP6; PET; beta cells; imaging reagents; islet transplantation; stem cell‐derived islets

DOI: https://doi.org/10.1111/dom.71343

Adv Healthc Mater. 2026 Sep 20. e71747

Click-Chemistry Functionalized Lipid Nanoparticles for In Vitro and In Vivo Transfection of Primary Human CD4+ T Cells.

Maaike De Cock, Elianne Burg, Sarah Gerlo, Linos Vandekerckhove, Bruno G De Geest, Jolien Van Cleemput.

CD4+ T cells orchestrate adaptive immunity and strategies that enable their genetic reprogramming hold promise for treating cancer, immune dysregulation and infectious diseases such as HIV. However, current T cell engineering approaches rely heavily on ex vivo manipulation, which is labor-intensive, costly, and can alter cell phenotypes. Lipid nanoparticles (LNPs) offer a scalable nonviral alternative, yet conventional formulations show minimal interaction with lymphocytes and are rapidly cleared by the liver. In this study, we develop a modular DBCO-azide click-chemistry approach to functionalize LNPs with a high-affinity CD4 nanobody, enabling precise CD4 receptor-directed delivery to human CD4+ T cells. Optimized CD4-targeted LNPs transfect up to 48% of non-activated CD4+ T cells within a PBMC co-culture, the highest efficiency reported so far through LNP transfection. Moreover, they successfully deliver CRISPR-Cas9 components to activated CD4+ T cells and achieve up to 32% gene editing. In humanized NSG-SGM3 mice, CD4-targeted LNPs selectively associate with and transfect circulating and bone marrow-resident human CD4+ T cells while showing minimal off-target activity in murine cells. These results establish CD4-nanobody LNPs as a versatile platform for targeted mRNA and gene-editing delivery, with broad potential for cancer immunotherapy, T cell reprogramming, and HIV cure strategies.

Keywords: T cells; gene editing; humanized mice; lipid nanoparticles; mRNA; targeted mRNA delivery

DOI: https://doi.org/10.1002/adhm.71747