Medical Data Science English

Targeting fibroblast activation protein in solid tumors via CAR-mRNA delivery promotes durable regression in solid tumor models (Scientific Reports, 2025)

In an international collaboration, Dr. Meng investigated CAR-T therapy holds great promise for solid tumors but is limited by the hostile tumor microenvironment and unstable target antigens. We developed an mRNA therapy that programs host immune cells in vivo to express a FAP-targeting CAR and attack cancer-associated fibroblasts. In multiple solid tumor models, this strategy—enhanced by chemotherapy and checkpoint blockade—drove strong tumor regression and long-lasting immune memory. The modified CAR mRNA boosted the speed and magnitude of responses, while inhibiting a cytokine pathway further relieved immunosuppression. Patient-derived xenografts revealed transcription factor network as biomarkers of resistance. These results show that a controllable, mRNA-based approach to remodeling the tumor stroma can unlock broader, more effective use of CAR-T therapy across solid cancers.

Deficiencies in methionine, tryptophan, and niacin remodels intestinal transcriptome and gut microbiota in mice (Scientific Reports, 2025)

In an international and academia–industry collaboration, Dr. Hara investigated the impact of essential amino acids on the gut microbiota in mice. While restriction of specific nutrients can recapitulate the benefits of caloric restriction, their intestinal effects remain poorly understood. Transient deprivation of methionine, tryptophan, and niacin reprogrammed oxidative phosphorylation pathways, expanded intestinal immune cells, and shifted gut microbial composition with increased Lactobacillus. These findings highlight nutrient restriction as a powerful lever to rewire host–microbiome interactions, offering fresh insights into cancer, inflammatory, autoimmune, neurodegenerative, and aging-related diseases.

N6-methyladenosine modification and significance in pancreatic cance (Cancer Med, 2025)

Dr. Hara highlighted the significance of RNA modifications in the diagnosis and therapy against solid cancers, indicating that the challenges and future optimization directions of this cancer medicine are explored, providing new perspectives and strategies for pancreatic cancer.

Antisense oligonucleotide targeting nicotinamide N-methyltransferase (Mol. Ther. Nuc. Acid., 2025)

In collaboration with Dr. Obika, Dr. Hara investigated antisense oligonucleotides targeting one-carbon metabolism in cancer as a novel molecular therapeutic strategy, which led to tumor inhibition.

In vivo engineered CAR-T cell therapy: lessons built from COVID-19 mRNA vaccines (Int J Mol Sci, 2025)

In an academia-industry collaboration, Dr. Meng indicated the significance and implication of in vivo engineered CAR-T cell therapy. By bridging RNA-based technological insights, CAR-T therapy in vivo may evolve into a versatile and accessible treatment paradigm across diverse oncological landscapes.

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