98%
921
2 minutes
20
We describe the repurposing and optimization of the TK-positive (thymidine kinase) vaccinia virus strain ACAM1000/ACAM2000™ as an oncolytic virus. This virus strain has been widely used as a smallpox vaccine and was also used safely in our recent clinical trial in patients with advanced solid tumors and Acute Myeloid Leukemia (AML). The vaccinia virus was amplified in CV1 cells and named CAL1. CAL1 induced remarkable oncolysis in various human and mouse cancer cells and preferentially amplified in cancer cells, supporting the use of this strain as an oncolytic virus. However, the therapeutic potential of CAL1, as demonstrated with other oncolytic viruses, is severely restricted by the patients' immune system. Thus, to develop a clinically relevant oncolytic virotherapy agent, we generated a new off-the-shelf therapeutic called Supernova1 (SNV1) by loading CAL1 virus into allogeneic adipose-derived mesenchymal stem cells (AD-MSC). Culturing the CAL1-infected stem cells allows the expression of virally encoded proteins and viral amplification prior to cryopreservation. We found that the CAL1 virus loaded into AD-MSC was resistant to humoral inactivation. Importantly, the virus-loaded stem cells (SNV1) released larger number of infectious viral particles and virally encoded proteins, leading to augmented therapeutic efficacy in vitro and in animal tumor models.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777144 | PMC |
http://dx.doi.org/10.3390/cancers14246136 | DOI Listing |
J Mol Histol
September 2025
Department of Urology, Yantai Yuhuangding Hospital, Qingdao University, No. 20 East Yuhuangding Road, Yantai, 264000, Shandong, China.
The stress urinary incontinence (SUI) is a difficulty in urology and current sub-urethral sling treatments are associated with inflamation and recurrence. In this study, we developed a novel tissue-engineered sling with myogenic induced adiposederived stem cells (MI-ADSCs) sheets induced by 5-Aza and combined with electrospun scaffolds of silk fibroin and poly(lactide-co-glycolide) (SF/PLGA) for the treatment of stress urinary incontinence. MI-ADSCs increased α-SMA, MyoD and Desmin the mRNA and protein expression.
View Article and Find Full Text PDFCalcif Tissue Int
September 2025
FirmoLab, Fondazione F.I.R.M.O. Onlus and Stabilimento Chimico Farmaceutico Militare (SCFM), 50141, Florence, Italy.
X-linked hypophosphatemia (XLH) is a rare and progressive disease, due to inactivating mutations in the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. These pathogenic variants result in elevated circulating levels of fibroblast growth factor 23 (FGF23), responsible for the main clinical manifestations of XLH, such as hypophosphatemia, skeletal deformities, and mineralization defects. However, XLH also involves muscular disorders (muscle weakness, pain, reduced muscle density, peak strength, and power).
View Article and Find Full Text PDFNat Aging
September 2025
Aging Biomarker Consortium (ABC), Beijing, China.
The global surge in the population of people 60 years and older, including that in China, challenges healthcare systems with rising age-related diseases. To address this demographic change, the Aging Biomarker Consortium (ABC) has launched the X-Age Project to develop a comprehensive aging evaluation system tailored to the Chinese population. Our goal is to identify robust biomarkers and construct composite aging clocks that capture biological age, defined as an individual's physiological and molecular state, across diverse Chinese cohorts.
View Article and Find Full Text PDFEMBO Mol Med
September 2025
Institute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, National Stem Cell Translational Resource Center & Ministry of Education Stem Cell Resource Center, Frontier Science Center for Stem Cell Research, School of Li
Primary microcephaly, a rare congenital condition characterized by reduced brain size, occurs due to impaired neurogenesis during brain development. Through whole-exome sequencing, we identified compound heterozygous loss-of-function mutations in CENTRIN 3 (CETN3) in a 5-year-old patient with primary microcephaly. As CETN3 has not been previously linked to microcephaly, we investigated its potential function in neurodevelopment in human pluripotent stem cell-derived cerebral organoids.
View Article and Find Full Text PDFEMBO Rep
September 2025
Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK post, Bellary Road, Bangalore, Karnataka, 560065, India.
Immune cells are increasingly recognized as nutrient sensors; however, their developmental role in regulating growth under homeostasis or dietary stress remains elusive. Here, we show that Drosophila larval macrophages, in response to excessive dietary sugar (HSD), reprogram their metabolic state by activating glycolysis, thereby enhancing TCA-cycle flux, and increasing lipogenesis-while concurrently maintaining a lipolytic state. Although this immune-metabolic configuration correlates with growth retardation under HSD, our genetic analyses reveal that enhanced lipogenesis supports growth, whereas glycolysis and lipolysis are growth-inhibitory.
View Article and Find Full Text PDF