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10.3389/fimmu.2017.01417

http://scihub22266oqcxt.onion/10.3389/fimmu.2017.01417
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C5672503!5672503!29163493
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suck abstract from ncbi


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pmid29163493      Front+Immunol 2017 ; 8 (ä): ä
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  • Alpha-Galactosylceramide/CD1d-Antibody Fusion Proteins Redirect Invariant Natural Killer T Cell Immunity to Solid Tumors and Promote Prolonged Therapeutic Responses #MMPMID29163493
  • Zhang L; Donda A
  • Front Immunol 2017[]; 8 (ä): ä PMID29163493show ga
  • Major progress in cancer immunotherapies have been obtained by the use of tumor targeting strategies, in particular with the development of bi-functional fusion proteins such as ImmTacs or BiTes, which engage effector T cells for targeted elimination of tumor cells. Given the significance of invariant natural killer T (iNKT) cells in bridging innate and adaptive immunity, we have developed a bi-functional protein composed of the extracellular part of CD1d molecule that was genetically fused to an scFv fragment from high affinity antibodies against HER2 or CEA. Systemic treatments with the CD1d-antitumor fusion proteins loaded with the agonist alpha-galactosylceramide (?GalCer) led to specific iNKT cell activation, resulting in a sustained growth inhibition of established tumors expressing HER2 or CEA, while treatment with the free ?GalCer was ineffective. Importantly, we discovered that ?GalCer/CD1d-antitumor fusion proteins were able to maintain iNKT cells reactive to multiple re-stimulations in contrast to their anergic state induced after a single injection of free ?GalCer. We further demonstrated that the antitumor effects by ?GalCer/CD1d-antitumor fusion proteins were largely dependent on the iNKT cell-mediated transactivation of NK cells. Moreover, prolonged antitumor effects could be obtained when combining the CD1d-antitumor fusion protein treatment with a therapeutic peptide/CpG cancer vaccine, which favored the capacity of iNKT cells to transactivate cross-presenting DCs for efficient priming of tumor-specific CD8 T cells. We will also summarize these pre-clinical results with a special focus on the cellular mechanisms underlying iNKT cell unresponsiveness to antigen re-challenge. Finally, we will discuss the perspectives regarding iNKT cell-mediated tumor targeting strategy in cancer immunotherapy.
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