Natural killer cells (NK cells) are the first line of the innate immune defense system, primarily located in peripheral circulation and lymphoid tissues. They kill virally infected and malignant cells through a balancing play of inhibitory and stimulatory receptors. In pre-clinical investigational studies, NK cells show promising anti-tumor effects and are used in adoptive transfer of activated and expanded cells, . NK cells express co-stimulatory molecules that are attractive targets for the immunotherapy of cancers. Recent clinical trials are investigating the use of CAR-NK for different cancers to determine the efficiency. Herein, we review NK cell therapy approaches (NK cell preparation from tissue sources, ways of expansion for "off-the-shelf" allogeneic cell-doses for therapies, and how different vector delivery systems are used to engineer NK cells with CARs) for cancer immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2021.732135 | DOI Listing |
Nat Protoc
January 2025
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
The clinical potential of current chimeric antigen receptor-engineered T (CAR-T) cell therapy is hampered by its autologous nature that poses considerable challenges in manufacturing, costs and patient selection. This spurs demand for off-the-shelf therapies. Here we introduce an ex vivo feeder-free culture method to differentiate gene-engineered hematopoietic stem and progenitor (HSP) cells into allogeneic invariant natural killer T (NKT) cells and their CAR-armed derivatives (CAR-NKT cells).
View Article and Find Full Text PDFMol Ther
January 2025
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, 53715, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, Wisconsin, 53715, USA; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, 53715, USA. Electronic address:
Natural killer (NK) cells are an appealing off-the-shelf, allogeneic cellular therapy due to their cytotoxic profile. However, their activity against solid tumors remains suboptimal in part due to the upregulation of NK-inhibitory ligands, such as HLA-E, within the tumor microenvironment. Here, we utilize CRISPR-Cas9 to disrupt the KLRC1 gene (encoding the HLA-E-binding NKG2A receptor) and perform non-viral insertion of a GD2-targeting chimeric antigen receptor (CAR) within NK cells isolated from human peripheral blood.
View Article and Find Full Text PDFStem Cell Res Ther
January 2025
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, 10F., Teaching & Research Building, Shuang-Ho Campus, No. 301, Yuantong Rd., Zhonghe Dist., Taipei, 235, Taiwan.
Chronic liver diseases, including cirrhosis and liver failure, remain formidable challenges due to their complex progression and limited therapeutic options. Mesenchymal stem cell (MSC) therapy has emerged as a game-changing approach, leveraging its potent immunomodulatory, anti-fibrotic, and regenerative capabilities, along with the ability to transdifferentiate into hepatocytes. This review delves into the latest advances in MSC-based treatments for chronic and end-stage liver diseases, as highlighted in current clinical trials.
View Article and Find Full Text PDFiScience
January 2025
Sana Biotechnology Inc., 1 Tower Place, South San Francisco, CA, USA.
Hypoimmune (HIP) allogeneic cell therapeutics hold the promise to allow off-the-shelf treatments for a broad patient population. Our HIP approach includes the depletion of major histocompatibility complex (MHC) class I and II molecules and the overexpression of Cd47. Here, we report the engineering of HIP mice that stably exhibit the HIP phenotype in all cell types.
View Article and Find Full Text PDFJ Funct Biomater
December 2024
Biotechnology Research Institute, Samara State Medical University, 443079 Samara, Russia.
Mandibular bone defect reconstruction remains a significant challenge for surgeons worldwide. Among multiple biodegradable biopolymers, allogeneic bone scaffolds derived from human sources have been used as an alternative to autologous bone grafts, providing optimal conditions for cell recruitment, adhesion, and proliferation and demonstrating significant osteogenic properties. This study aims to investigate the bone microstructure of the human scapula as a source for allogeneic bone scaffold fabrication for mandibular tissue engineering purposes.
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