Development of CAR (Chimeric Antigen Receptor) - NK cells against Glioblastoma stem cells.

• Grant number: 22/05072-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2025
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Oswaldo Keith Okamoto
• Grantee: Vitória Alves de Lima
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Glioblastoma (GBM) is the most frequent and aggressive primary malignant tumor that affects the Central Nervous System (CNS) in adults. Currently, treatment consists of surgical removal of the tumor, radiotherapy and chemotherapy, and yet the median survival of patients after diagnosis is around 15 months. Recent advances in cell therapies have increased the success in the treatment of genetic diseases, through the genetic manipulation of autologous or allogeneic cells and subsequent injection in the patient, for restoration of defective cells, delivery of drugs to specific sites and even acting directly against neoplastic cells. The development of Chimeric Antigen Receptors (CAR) has shown to be a promising technology for the identification and elimination of tumor cells, where immune system cells, such as T lymphocytes (pioneers) and Natural Killer (NK) cells, are modified to express a receptor for specific tumor antigens, aiming to increase their antitumor activity. The use of this technique in NK cells has advantages over T cells due to their unique properties, such as the recognition and elimination of tumor cells independently of the human leukocyte antigen system (HLA) and T cell receptors (TCRs), and even the identification of cells that lack HLA proteins, which would normally evade the patient's adaptive immune system; also present a lower risk in allogeneic transplants due to the absence of TCRs, and even lower chances of neurotoxicity, in part due to the spectrum of cytokines secreted by these cells. The present project proposes the development of a CAR receptor for NK cells (CAR-NK) targeting two antigens expressed in GBM tumor stem cells (TSC) that have strong potential as therapeutic targets, aiming at a new immunotherapeutic approach for future clinical application.