Since the approval in 2017 and the outstanding success of Kymriah® and Yescarta®, the number of clinical trials investigating the safety and efficacy of chimeric antigen receptor-modified autologous T cells has been constantly rising. Currently, more than 200 clinical trials are listed on clinicaltrial.gov. In contrast to CAR-T cells, natural killer (NK) cells can be used from allogeneic donors as an "off the shelf product" and provide alternative candidates for cancer retargeting. This review summarises preclinical results of CAR-engineered NK cells using both primary human NK cells and the cell line NK-92, and provides an overview about the first clinical CAR-NK cell studies targeting haematological malignancies and solid tumours, respectively.
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http://dx.doi.org/10.1159/000495771 | DOI Listing |
Mol Cancer
January 2025
Department of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, 400042, China.
As research progresses, our understanding of the tumor microenvironment (TME) has undergone profound changes. The TME evolves with the developmental stages of cancer and the implementation of therapeutic interventions, transitioning from an immune-promoting to an immunosuppressive microenvironment. Consequently, we focus intently on the significant role of the TME in tumor proliferation, metastasis, and the development of drug resistance.
View Article and Find Full Text PDFNPJ Vaccines
January 2025
Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH, USA.
Natural killer (NK) cell-driven effector mechanisms, such as antibody-dependent cell-mediated cytotoxicity, emerged as a secondary correlate of protection in the RV144 HIV vaccine clinical trial, the only vaccine thus far demonstrating some efficacy in human trials. Therefore, leveraging NK cells with enhanced cytotoxic effector responses may bolster vaccine-induced protection against HIV. Here, we investigated the effect of orally administering indole-3-carbinol (I3C), an aryl hydrocarbon receptor (AHR) agonist, as an adjuvant to an RV144-like vaccine platform in a mouse model.
View Article and Find Full Text PDFBackground: FT596 is an induced pluripotent stem-cell (iPSC)-derived chimeric antigen receptor (CAR) natural killer (NK) cell therapy with three antitumour modalities: a CD19 CAR; a high-affinity, non-cleavable CD16 Fc receptor; and interleukin-15-interleukin-15 receptor fusion. In this study, we aimed to determine the recommended phase 2 dose (RP2D) and evaluate the safety and tolerability of FT596 as monotherapy and in combination with rituximab. We also aimed to evaluate the antitumour activity and characterise the pharmacokinetics of FT596 as monotherapy and in combination with rituximab.
View Article and Find Full Text PDFStructure
January 2025
Novartis Biomedical Research, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA. Electronic address:
Inflammatory bowel disease (IBD) consists of chronic conditions that severely impact a patient's health and quality of life. Interleukin-10 (IL-10), a potent anti-inflammatory cytokine has strong genetic links to IBD susceptibility and has shown strong efficacy in IBD rodent models, suggesting it has great therapeutic potential. However, when tested in clinical trials for IBD, recombinant human IL-10 (rhIL-10) showed weak and inconsistent efficacy due to its short half-life and pro-inflammatory properties that counteract the anti-inflammatory efficacy.
View Article and Find Full Text PDFSTAR Protoc
January 2025
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. Electronic address:
Standard flow cytometry-based assays can determine the cytotoxicity of immune effector cells, but it is challenging to monitor the dynamic processes of cytotoxicity. Here, we present a protocol for continuous observation of natural killer (NK) cell-mediated cytotoxicity with microwell arrays using an automated microscope. We describe steps for isolating and labeling primary NK cells, loading cells onto microwell arrays, monitoring target wells, and image analysis.
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