Background/Objectives: An overwhelming burden to clinics, herpes zoster (HZ), or shingles, is a painful disease that occurs frequently among aged individuals with a varicella-zoster virus (VZV) infection history. The cause of shingles is the reactivation of dormant VZV in the dorsal root ganglia/cranial nerves of the human body. Patients with HZ experience sharp, intense, electric shock-like pain, which makes their health-related quality of life (HRQoL) extremely low. Methods: Various mRNA constructs were designed based on intracellular organelle-targeting strategies and AI algorithm-guided high-throughput automation platform screening and were then synthesized by in vitro transcription and encapsulated with four-component lipid nanoparticles (LNPs). Immunogenicity was evaluated on a naïve mouse model, long-term mouse model, and VZV-primed mouse model. Safety was evaluated by a modified "nestlet shredding" method for potential adverse effects induced by vaccines. Comparison between muscular and intradermal administrations was conducted using different inoculated approaches as well. Results: The best vaccine candidate, CVG206, showed robust humoral and cellular immune responses, durable immune protection, and the fewest adverse effects. The CVG206 administered intradermally revealed at least threefold higher humoral and cellular immune responses compared to intramuscular vaccination. The manufactured and lyophilized patch of CVG206 demonstrated good thermal stability at 2-8 °C during 9 months of storage. Conclusions: The lyophilized mRNA vaccine CVG206 possesses remarkable immunogenicity, long-term protection, safety, and thermal stability, and its effectiveness could even be further improved by intradermal administration, revealing that CVG206 is a promising vaccine candidate for HZ in future clinical studies.

In the last decade, advancements in understanding the genetic landscape of lung squamous cell carcinoma (LUSC) have significantly impacted therapy development. Immune checkpoint inhibitors (ICI) have shown great promise, improving overall and progression-free survival in approximately 25% of the patients. However, challenges remain, such as the lack of predictive biomarkers, difficulties in patient stratification, and identifying mechanisms that cancers use to become immune-resistant ("immune-cold"). Analysis of TCGA datasets reveals reduced MAP1LC3C expression in cancer. Further analysis indicates that low MAP1LC3C is associated with reduced CIITA and HLA expression and with decreased immune cell infiltration. In tumor cells, silencing MAP1LC3C inhibits CIITA expression and suppresses HLA class II production. These findings suggest that cancer cells are selected for low MAP1LC3C expression to evade efficient immune responses.
Copyright: © 2025 Barbeau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Antibody-drug conjugates (ADCs) combining monoclonal antibodies with cytotoxic payloads are a rapidly emerging class of immune-based therapeutics with the potential to improve the treatment of cancer, including children with relapse/refractory acute lymphoblastic leukemia (ALL). CD123, the α subunit of the interleukin-3 receptor, is overexpressed in ALL and is a potential therapeutic target. Here, we show that pivekimab sunirine (PVEK), a recently developed ADC comprising the CD123-targeting antibody, G4723A, and the cytotoxic payload, DGN549, was highly effective in vivo against a large panel of pediatric ALL patient-derived xenograft (PDX) models (n = 39). PVEK administered once weekly for 3 weeks resulted in a median event-free survival (EFS) of 57.2 days across all PDXs. CD123 mRNA and protein expression was significantly higher in B-lineage (n = 65) compared with T-lineage (n = 25) ALL PDXs (p < 0.0001), and mice engrafted with B-lineage PDXs achieved significantly longer EFS than those engrafted with T-lineage PDXs (p < 0.0001). PVEK treatment also resulted in significant clearance of human leukemia cells in hematolymphoid organs in mice engrafted with B-ALL PDXs. Notably, our results showed no direct correlation between CD123 expression and mouse EFS, indicating that CD123 is necessary but not sufficient for in vivo PVEK activity. Importantly, a PDX with very high CD123 cell surface expression but resistant to in vivo PVEK treatment, failed to internalize the G4723A antibody while remaining sensitive to the PVEK payload, DGN549, suggesting a novel mechanism of resistance. In conclusion, PVEK was highly effective against a large panel of B-ALL PDXs supporting its clinical translation for B-lineage pediatric ALL.
© 2025 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.

Galectins are a group of carbohydrate-binding proteins with a presumed immunomodulatory role and an elusive function on antigen-presenting cells. Here we analyzed the expression of galectin-1 and found upregulation of galectin-1 in the extracellular matrix across multiple tumors. Performing an in-depth and dynamic proteomic and phosphoproteomic analysis of human macrophages stimulated with galectin-1, we show that galectin-1 induces a tumor-associated macrophage phenotype with increased expression of key immune checkpoint protein programmed cell death 1 ligand 1 (PD-L1/CD274) and immunomodulator indoleamine 2,3-dioxygenase-1 (IDO1). Galectin-1 induced IDO1 and its active metabolite kynurenine in a dose-dependent manner through JAK/STAT signaling. In a 3D organotypic tissue model system equipped with genetically engineered tumorigenic epithelial cells, we analyzed the cellular source of galectin-1 in the extracellular matrix and found that galectin-1 is derived from epithelial and stromal cells. Our results highlight the potential of targeting galectin-1 in immunotherapeutic treatment of human cancers.
© 2023 The Authors.

Introduction: Adipose tissue is widely exploited in regenerative medicine thanks to its trophic properties, mainly based on the presence of adipose-derived stromal cells. Numerous devices have been developed to promote its clinical use, leading to the introduction of one-step surgical procedures to obtain minimally manipulated adipose tissue derivatives. However, only a few studies compared their biological properties. This study aimed to characterize micro-fragmented (MAT) and nanofat adipose tissue (NAT) obtained with two different techniques. Methods: MAT, NAT and unprocessed lipoaspirate were collected from surgical specimens. RNA extraction and collagenase isolation of stromal vascular fraction (SVF) were performed. Tissue sections were analysed by histological and immunohistochemical (collagen type I, CD31, CD34 and PCNA) staining to assess tissue morphology and cell content. qPCR was performed to evaluate the expression of stemness-related (SOX2, NANOG and OCT3/4), extracellular matrix (COL1A1) and inflammatory genes (IL1β, IL6 and iNOS). Furthermore, multilineage differentiation was assessed following culture in adipogenic and osteogenic media and staining with Oil Red O and Alizarin red. ASC immunophenotype was assessed by flow cytometric analysis of CD90, CD105, CD73 and CD45. Results: Histological and immunohistochemical results showed an increased amount of stroma and a reduction of adipocytes in MAT and NAT, with the latter displaying the highest content of collagen type I, CD31, CD34 and PCNA. From LA to MAT and NAT, an increasing expression of NANOG, SOX2, OCT3/4, COL1A1 and IL6 was noted, while no significant differences in terms of IL1β and iNOS emerged. No statistically significant differences were noted between NAT and SVF in terms of stemness-related genes, while the latter demonstrated a significantly higher expression of stress-related markers. SVF cells derived from all three samples (LA, MAT, and NAT) showed a similar ASC immunoprofile as well as osteogenic and adipogenic differentiation. Discussion: Our results showed that both MAT and NAT techniques allowed the rapid isolation of ASC-rich grafts with a high anabolic and proliferative potential. However, NAT showed the highest levels of extracellular matrix content, replicating cells, and stemness gene expression. These results may provide precious clues for the use of adipose tissue derivatives in the clinical setting.
Copyright © 2023 Cicione, Vadalà, Di Giacomo, Tilotta, Ambrosio, Russo, Zampogna, Cannata, Papalia and Denaro.