Development of a chimeric antigen receptor for application on glioblastoma treatment

• Grant number: 21/00689-5
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2021
• Effective date (End): January 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Oswaldo Keith Okamoto
• Grantee: Thiago Giove Mitsugi
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center, AP.CEPID

Abstract

Gliomas are the most common Central Nervous System tumors around the globe and comprehend up to 80% of all malignant primary brain tumors. Throughout the types of gliomas, glioblastomas multiforme stand out as the most aggressive and common type. The currently available therapies for glioblastoma treatment are insufficient, and consist of medical resection followed by chemo/radiotherapy and, yet, result in a overall survival of less than 2 years of these patients. The resistance to chemo/radiotherapy, as well as the capacity of glioblastomas to relapse, are assigned to the presence of tumor stem-cells. Several strategies aim to target tumor stem-cells specifically, based on their unique physiological and molecular features. Imunotherapy has emerged whitin oncology due to studies with Chimeric Antigen Receptors (CAR), with two recent aprovals from the FDA, in the USA, for therapies using CAR-T cells. The success of the CAR-T cell therapies rely extensively on the design of the receptor and specially the assignment of a correct tumoral target. In this sense, the present study aims to explore the therapeutic potential of a CAR capable of recognizing antigens aberrantly expressed on glioma stem cells. These antigens were demonstrated to broadly and consistently label glioma stem-cells, specially in glioblastomas. Glioma cells expressing this antigen were more aggressive and capable of enhanced tumorigenesis in vivo and in vitro, revealing the significance of this tumoral target. In that regard, we will design a CAR, that will be expressed on T lymphocytes. We will also evaluate whether these CAR-T cells are capable of specifically target and exert antitumoral activity against glioma stem cells. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MITSUGI, Thiago Giove. Role of the Saccharomyces cerevisiae antioxidant protein Ahp1 in the cellular response against oxidative stress. 2023. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) São Paulo.