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Chimeric antigen receptor (CAR) NK cells are demonstrating promising activity in clinical trials and possess a favorable safety profile compared to CAR-T cells. The Killer cell Immunoglobulin-like Receptors (KIR) have a critical role in the control of NK cell function, and recently, this family of activating and inhibitory receptors have been targeted to improve CAR-NK function. These strategies include the utilisation of inhibitory KIR to reduce trogocytosis-associated NK cell fratricide, the downregulation of inhibitory KIR on CAR-NK cells to alleviate HLA mediated suppression, the selection of CAR-NK cell donors enriched for activating KIR, and the use of activating KIR intracellular domains within novel CAR constructs. These pre-clinical studies demonstrate the potential utility of targeting the KIR to improve CAR-NK cell efficacy and patient outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615527 | PMC |
http://dx.doi.org/10.20517/jtgg.2023.25 | DOI Listing |
J Immunother Cancer
September 2025
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
Background: Patients with acute myeloid leukemia (AML) are often older, which brings challenges of endurance and persistent efficacy of autologous chimeric antigen receptor (CAR)-T cell therapies. Allogenic CAR-natural killer (NK) cell therapies may offer reduced toxicities and enhanced anti-leukemic potential against AML. CD33 CAR-NK cells have been investigated for AML therapy.
View Article and Find Full Text PDFInt Immunopharmacol
August 2025
Immunology Program, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China. Electronic address:
Patient-derived tumor organoids, often referred to as tumor organoids, serve as in vitro tumor models for tumor-related research, such as living biobanks, identification of biomarkers, drug screening and personalized precision medicine. Despite great success of chimeric antigen receptor (CAR)-engineered T cell therapy of B cell malignancies, the efficacy of receptor-engineered immune cell therapy of solid tumors remains suboptimal due to the molecular heterogeneity and immunosuppressive tumor microenvironment. Moreover, direct and extensive clinical studies are limited because of the toxicity of drugs or adoptively transferred immune cells.
View Article and Find Full Text PDFCancer Cell
August 2025
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Institute for Cell Therapy Discovery and Innovation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:
Adoptive cell therapy using engineered natural killer (NK) cells is a promising approach for cancer treatment, with targeted gene editing offering the potential to further enhance their therapeutic efficacy. However, the spectrum of actionable genetic targets to overcome tumor and microenvironment-mediated immunosuppression remains largely unexplored. We performed multiple genome-wide CRISPR screens in primary human NK cells and identified critical checkpoints regulating resistance to immunosuppressive pressures.
View Article and Find Full Text PDFBiochim Biophys Acta Rev Cancer
August 2025
Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha, Hunan, China; Academician Workstation for Oral-maxillofacial and Regenerative Medicine, Central South University, Changsha, Hunan, China. Electronic address:
Trogocytosis, derived from the Greek "trogo-," meaning "nibble," is a cellular process in which one cell extracts membrane fragments and surface molecules from another, modulating the functions of both donor and recipient cells. In tumor immunology, trogocytosis between immune cells and tumor cells exhibits paradoxical effects. Conflicting reports suggest it can enhance antitumor effects through processes like trogoptosis, antigen presentation, and beneficial antigen shaving, while facilitating protumor effects by antigen masking, immune cell exhaustion, immune cell fratricide, and detrimental antigen shaving.
View Article and Find Full Text PDFAdv Sci (Weinh)
August 2025
Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, 400030, China.
Immunotherapy, particularly chimeric antigen receptor T cell (CAR-T) therapy, has revolutionized the treatment of hematological malignancies and autoimmune diseases. However, its efficacy in solid tumors remains limited due to challenges such as tumor heterogeneity, an immunosuppressive microenvironment, and poor T cell infiltration. This review first summarizes the primary causes and challenges that restrict CAR-T therapy in the treatment of solid tumors, followed by an overview of recent advancements in gastric cancer, liver cancer, and glioma, where early trials have demonstrated promising clinical potential.
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