PN 23.16.02.02

The project proposes an innovative approach to a therapeutic method that is based on the NK cells are activated by cytokines, and the administration of an inhibitor of the receptor TGF-β, which may provide an improved method for the treatment of metastatic melanoma.

The purpose of the project is the establishment of the molecular profiling of NK cells for the monitoring of anti-tumor, and identification of new methods of immunotherapy in metastatic melanoma, in view of the current trends of the medicine and the accuracy in the advanced stages of cancer.

Objectives:

• The generation of NK cells are activated by cytokines
• Validation of in vitro activity, the increased antitumor activity of NK-cells are activated by cytokines, and treatment with an inhibitor of TGFBRI/S
• The validation of the in vivo activity of the crecute range of cells and NK are activated by cytokines, and treatment with an inhibitor of TGFBRI/II as a potential candidate for the treatment of cancer by using the models of murine melanoma

Expected results:
– Achieve cells and NK-cells with cytotoxic activity increased.
– The identification of potential molecular markers on NK cells for the monitoring of anti-tumour agent.
– The identification and evaluation of dosing regimens for optimal transfer is adopted for the cells and NK-cells in metastatic melanoma.
– The identification and evaluation of the optimal dose of TGFBRI/S for the management of pre-clinical for the treatment of metastatic melanoma.
– The validation of the possible solutions to the patients ' metastatic melanoma, based on the transfer adopted by the cells and NK-cells, and an inhibitor of TGFBRI/S.

Indicators

Communications

1. Role of the scavenger receptor CD36 in diet-induced obesity, and metastatic melanoma. Gheorghita Isvoranu, Mihaela Surcel, Adriana Narcisa Munteanu, Carolina Constantin, Marioara Chiritoiu-Butnaru, Monica Teodora Neagu. 19^th The European Association of Dermato Oncology Congress, Rome, Italy, 2023
2. Strain Differences in the Response to Analgesia in Mice. Isvoranu Gheorghita, Anghelache Laurențiu, Coman Cristin. 1st CELAS Congress, Prague, Czech Republic, 2023
3. The High-fat diet impairs phenotype and function of Natural Killer cells in melanoma-bearing mice. Isvoranu, Mihaela Surcel, Adriana Munteanu, Carolina Constantin, Monica Neagu. 3rd Edition of the OncoHub Conference and 1st OncoHub Preconference Workshop Event, Bucharest, Romania, 2023
4. The High-fat diet impairs phenotype and function of Natural Killer cells.Isvoranu, Mihaela Surcel, Adriana Munteanu, Carolina Constantin, Monica Neagu. International Pathology Conference of the Victor Babeș Institute, Bucharest, Romania, 2023
5. Animal research saves lives. Gheorghița Isvoranu. 8th ARSAL National Symposium, Bucharest, Romania, 2024
6. Effects of high fat diet on immune cells in the tumor-bearing mice. G Isvoranu, M Surcel, A Munteanu, C Constantin, M Neagu, M Chirițoiu-Butnaru. 8th ARSAL National Symposium, Bucharest, Romania, 2024
7. Immunological evaluation of fat in the diet-induced alterations in the Grasp55-/- mice.M Chiritoiu-Butnaru, G Chiritoiu, M Surcel, G Isvoranu. 8th ARSAL National Symposium, Bucharest, Romania, 2024
8. Inhibiting TGF-β signaling restores the function of cytokines-activated Natural Killer cells. G Isvoranu, AE Mândrilă, M Surcel, AN Munteanu, M Chirițoiu-Butnaru. The Annual International Conference of the RSBMB 2024, Bucharest, Roamania
9. Targeting the TGF-β signaling to reinforce the therapeutic potential of cytokines-activated Natural Killer cells as immunotherapy in cancerG Isvoranu, M Surcel, AN Munteanu, AM Enciu, E Codrici, G Chirițoiu, C Munteanu, AE Mândrilă, M Chirițoiu-Butnaru. International Pathology Conference of the Victor Babeș Institute Bucharest, Roamania, 2024
10. Transforming growth factor-beta-impacts of the Natural Killer cell functionality.G Isvoranu, AM Enciu, E Codrici, M Surcel, G Chirițoiu, M Chirițoiu-Butnaru. The annual scientific conference of the “Cantacuzino” Institute, Bucharest, Romania, 2024
11. Transforming growth factor-beta-impacts of the Natural Killer cell phenotype and functionality. Gheorghița Isvoranu, Mihaela Surcel, Ana-Maria Enciu, Elena Codrici, Gabriela Chirițoiu, Cristian Munteanu, Marioara Chirițoiu-Butnaru. 10th Symposium on Advances in Cancer Immunology and Immunotherapy, Larissa, Greece, 2024

12. Toll Like Receptor 7/8 agonists antitumor effects on NK cells in murine melanoma model, G. Isvoranu, M. Surcel, A. Munteanu, A.M. Enciu, M. Chiritoiu-Butnaru, G.Chiritoiu, C. Munteanu, M. Neagu. SEE J Immunol, vol 8 No CITIM (2025). DOI: https://doi.org/10.3889/seejim.2025.6135

13. Phenotypic and functional characteristics of NK cells from mice with lung metastases, G. Isvoranu, M. Surcel, A. Munteanu, A.M. Enciu, M. Chiritoiu-Butnaru, G. Chiritoiu, C. Munteanu, M. Neagu. A XVIII-a ediție a Congresului Național de Citometrie, București, România.

Publications 

1. The Therapeutic potential of interleukin-21 in cancer. G. Isvoranu, I Chiritoiu-The Military Academy. Front Immunol, 2024, 4:15:1369743, doi:10.3389/fimmu.2024.1369743
2.  Behavior testing in two different knockout mouse strains are related to chronic inflammation and oxidative stress. Dobre Ana Maria, Isvoranu Gheorghita, Enciu Ana-Maria, Hinescu Mihail Eugen. Cellular and molecular biology, 69(3);113-117. TWO 10.14715/wcc/2023.69.3.15