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GITRL enhances cytotoxicity and persistence of CAR-T cells in cancer therapy.
Mol Ther
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai, China, 200241. Electronic address:
CAR T-cell therapy has achieved remarkable clinical success in treating hematological malignancies. However, its clinical efficacy in solid tumors is less satisfactory, partially due to poor in vivo expansion and limited persistence of CAR-T cells. Here, we demonstrated that the overexpression of glucocorticoid-induced tumor necrosis factor receptor-related protein ligand (GITRL) enhances the anti-tumor activity of CAR-T cells.
View Article and Find Full Text PDFMultiple gene-deletion vaccinia virus Tiantan strain against mpox.
Virol J
January 2025
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, People's Republic of China.
Monkeypox virus (MPXV) is an important zoonotic pathogenic virus, which poses serious threats to public health. MPXV infection can be prevented by immunization against the variola virus. Because of the safety risks and side effects of vaccination with live vaccinia virus (VACV) strain Tian Tan (VTT), we constructed two gene-deleted VTT recombinants (TTVAC7 and TTVC5).
View Article and Find Full Text PDFNovel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer.
Sci Rep
January 2025
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and α-smooth muscle (α-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro.
View Article and Find Full Text PDFThe α-globin super-enhancer acts in an orientation-dependent manner.
Nat Commun
January 2025
Gene Regulation Laboratory, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS, Oxford, UK.
Individual enhancers are defined as short genomic regulatory elements, bound by transcription factors, and able to activate cell-specific gene expression at a distance, in an orientation-independent manner. Within mammalian genomes, enhancer-like elements may be found individually or within clusters referred to as locus control regions or super-enhancers (SEs). While these behave similarly to individual enhancers with respect to cell specificity, distribution and distance, their orientation-dependence has not been formally tested.
View Article and Find Full Text PDFDivergent transcriptional states and kinetics of circulating tumor-infiltrating lymphocyte repertoires with highly homologous T-cell receptor sequences in a patient during immunotherapy.
J Immunother Cancer
January 2025
Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
Evidence has shown that T-cell receptors (TCRs) that recognize the same epitopes may not be the exact TCR clonotypes but have slightly different TCR sequences. However, the changes in the genomic and transcriptomic signatures of these highly homologous T cells during immunotherapy remain unknown. Here, we examined the evolutionary features in circulating TCR clonotypes observed in tumors (tumor-infiltrating lymphocyte (TIL)-TCRs) by combining single-cell RNA/TCR sequencing of longitudinal blood samples and TCR sequencing of tumor tissue from a patient treated with anti-cytotoxic T-lymphocyte-associated protein 4/programmed cell death protein-1 therapy.
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