PN-IV-P2-2.1-I-2023-1169

Abstract

Scientific context: Metastasis is the main cause of death in cancer and is in need of a great deal of effort in order to manage this disease. Innate ability of NK cells to eliminate tumor cells has made them the best candidate for the immunotherapy of cancer, imunoterapiile are based on your cells and NK have been researched for years. The development and the progression of the cancer is determined by the relationship between the tumor and the immune system of the host, a number of mechanisms that contribute to the suppression of cellular immunity. One of the most important mechanism is the production of cytokine inhibitors such as TGF-β. This cytokine can affect strongly the activity of NK cells, reducing the ability of the citotoxica, and by affecting the activity of anti-tumour. Foreclosure or the loss of receiver of type 2 TGF-β on NK cells could restore the function of the citotoxica.

PurposeThis project aims to develop the NK cells knockdown for TGFR2 activated by the cytokine with antitumor activity improved in order to control the progression of cancer and metastasis.

NK cells will be genetically modified by the technology of CRISPR/Cas9 to remove the lashes TGFR2, which will provide resistance to the inhibitory effect exerted by TGF-β. NK cells knockdown for TGFR2 will be activated by the complex of the other in order to gain the strength and functions of cells increased. Cells and NK-cells, genetically modified, will be made available on the models of murine melanoma.

OBJECTIVES AND RESULTS

Goals

Q1. The generation of NK cells knockdown for TGFBR2, which can be activated by cytokines

O2. Validarea in vitro a activității antitumorale îmbunătățite a celulelor NK knockout pentru TGFBR2 activate cu citokine

O3. The validation of the NK cells knockdown for TGFBR2 are activated by cytokines as a potential candidate, you've been doing for the treatment of cancer by using models, pictures of a mouse