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The bispecific immunoligand ULBP2-aCEA redirects natural killer cells to tumor cells and reveals potent anti-tumor activity against colon carcinoma. | LitMetric

AI Article Synopsis

  • NKG2D is a receptor on NK and T cells that plays a key role in detecting and fighting tumors, specifically explored for its potential in colon cancer treatment through the ligand ULBP2.
  • The researchers created a fusion protein combining ULBP2 with an antibody that targets a specific tumor marker (CEA), effectively guiding NK cells to attack cancer cells.
  • This approach showed promising results in mice, leading to delayed tumor growth and increased immune cell activity, suggesting a new immunotherapy strategy for treating solid tumors.

Article Abstract

NKG2D, an activating receptor expressed on NK cells and T cells, is critically involved in tumor immunosurveillance. In this study, we explored the potential therapeutic utility of the NKG2D ligand ULBP2 for the treatment of colon carcinoma. To this end we designed a fusion protein consisting of human ULBP2 and an antibody-derived single chain targeting the tumor carcinoembryonic antigen (CEA). The bispecific recombinant fusion protein re-directed NK cells towards malignant cells by binding to both, tumor cells and NK cells, and triggered NK cell-mediated target cell killing in vitro. Moreover, tumor growth was significantly delayed in a syngeneic colon carcinoma mouse model in response to immunoligand treatment. The anti-tumor activity could be attributed to the stimulation of immune cells with an elevated expression of the activation marker CD69 on NK, T and NKT cells and the infiltration of CD45+ immune cells into the solid tumor. In summary, it was demonstrated that immunoligands provide specific tumor targeting by NK cells and exert anti-tumor activity in vitro and in vivo. This technology represents a novel immunotherapeutic strategy for solid tumors with the potential to be further developed for clinical applications.

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Source
http://dx.doi.org/10.1002/ijc.28609DOI Listing

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