Publications by authors named "J Eitler"
NK cells are endowed with tumor killing ability, nevertheless most cancers impair NK cell functionality, and cell-based therapies have limited efficacy in solid tumors. How cancers render NK cell dysfunctional is unclear, and overcoming resistance is an important immune-therapeutic aim. Here, we identify autophagy as a central regulator of NK cell anti-tumor function.
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- Radiation-induced morphea (RIM) is an uncommon complication of radiotherapy, mainly seen in breast cancer patients, characterized by inflammatory fibrosis where the underlying mechanisms are not well understood.
- The study focused on analyzing fibroblasts from RIM patients to find potential therapeutic targets, discovering key differences like increased alpha-smooth-muscle-actin (αSMA) and Myc activation in RIM fibroblasts.
- Treatment with the anti-inflammatory drug mesalazine was shown to effectively improve patient symptoms by reversing the harmful fibroblast changes and significantly reducing levels of the biomarker osteopontin (OPN).
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- NK cells can be made more effective against tumors through targeting with antibodies or genetic modifications, but some tumors still resist attacks, particularly in the context of the ErbB2 (HER2) antibody trastuzumab.
- In experiments, using NK-92 cells and primary human NK cells, functions like cell killing and cytokine release were diminished when LFA-1 was blocked or ICAM-1 was absent during ADCC triggered by trastuzumab, but CAR-engineered NK cells showed resilience against these disruptions.
- The study found that while trastuzumab needed LFA-1 to fully activate NK cells, the ErbB2-CAR provided a strong activation on its own, leading to effective tumor targeting, and
Natural killer (NK) cells are attractive effectors for adoptive immunotherapy of cancer. Results from first-in-human studies using chimeric antigen receptor (CAR)-engineered primary NK cells and NK-92 cells are encouraging in terms of efficacy and safety. In order to further improve treatment strategies and to test the efficacy of CAR-NK cells in a personalized manner, preclinical screening assays using patient-derived tumor samples are needed.
View Article and Find Full Text PDFIntroduction: Natural killer 92 (NK-92) cells are an attractive therapeutic approach as alternative chimeric antigen receptor (CAR) carriers, different from T cells, once they can be used in the allogeneic setting. The modest outcomes observed with NK-92 cells continue to present hurdles in successfully translating NK-92 cell therapies into clinical applications. Adoptive transfer of CAR-NK-92 cells holds out the promise of therapeutic benefit at a lower rate of adverse events due to the absence of GvHD and cytokine release syndrome.
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