Development of cellular immunotherapy for solid tumors using combined treatment with anti-GD2 gamma/delta CAR-T cells and alpha/beta CAR-T cells

• Grant number: 24/10871-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2024
• End date: May 31, 2027
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Lucas Eduardo Botelho de Souza
• Grantee: Mateus da Silva Matias Antunes
• Host Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil

Abstract

Therapy based on the adoptive transfer of T cells expressing chimeric antigen receptors (CAR) have been showing good results in safety and efficacy against B cell malignancies. However, efficacy is still limited in solid tumors, mainly due to mechanisms of immunosuppression, hypoxia , nutrient deprivation and low infiltration of immune cells in the tumor microenvironment. Therefore, a complementary and promising strategy would be to develop immunotherapies that combine different cells of the immune system with distinct and synergistic functions to overcome these biological barriers. Among cells of the immune system, gamma/delta T lymphocytes have desirable characteristics for cellular immunotherapy of solid tumors, such as greater infiltration capacity, cross-presentation of antigens, generation of memory cells and remodeling of the tumor microenvironment towards a permissive pro-inflammatory profile. to harness the antitumor immune response. Therefore, we hypothesize that gamma/delta T cells can be used in combination with alpha/beta CAR-T cells to enhance therapeutic efficacy against solid tumors. Therefore, the objective of this work is to generate and characterize the antitumor efficacy in vitro and in vivo gamma/delta T cells expressing an anti-GD2 CAR in a glioblastoma model, followed by combined administration with alpha/beta CAR-T cells expressing anti-GD2. GD2 to consolidate the antitumor response. We hope that the results of this project will lead to the generation of a new cellular immunotherapy approach for solid tumors. in addition to contributing to the nucleation and training of human resources in the area of advanced cell therapies.