Synergistic Anti-Glioblastoma Therapy via EGFRvIII-CAR-T Cells Combined with Pembrolizumab and Metformin
Project Description
Glioblastoma multiforme (GBM) is the most aggressive and lethal primary brain tumor in adults, with extremely limited therapeutic options and dismal patient prognosis. Epidermal growth factor receptor variant III (EGFRvIII), a tumor-specific mutation highly prevalent in GBM, has emerged as a promising target for chimeric antigen receptor T (CAR-T) cell therapy, a revolutionary immunotherapeutic strategy that enables engineered T cells to specifically recognize and eliminate tumor cells. However, the clinical efficacy of EGFRvIII-CAR-T cells is severely hindered by multiple bottlenecks, including the immunosuppressive and hypoxic GBM tumor microenvironment (TME), intrinsic CAR-T cell exhaustion, and tumor antigen escape. Single-agent or dual-combination therapies have failed to fully overcome these challenges, highlighting the urgent need for optimized multi-modal treatment strategies. The proposed research will focus on the in vitro exploration of the synergistic anti-tumor effects of a triple combination therapy comprising EGFRvIII-CAR-T cells, the anti-PD-1 immune checkpoint inhibitor pembrolizumab, and the metabolic modulator metformin. Participating students will be involved in key experimental steps, including the preparation and validation of EGFRvIII-CAR-T cells, the establishment of hypoxic co-culture models of GBM cells and CAR-T cells, and the assessment of therapeutic efficacy through multiple functional assays. This project will not only provide critical experimental evidence for the synergistic mechanisms of the triple combination therapy, laying a solid foundation for its subsequent preclinical and clinical translation, but also offer students valuable hands-on experience in cellular immunology, tumor biology, and gene engineering techniques.
Supervisor
LUO, Zhengtang
Quota
2
Course type
UROP1000
UROP1100
UROP2100
UROP3100
UROP3200
UROP4100
Applicant's Roles
1. Assist in the preparation and validation of EGFRvIII-CAR-T cells, including cell culture and transduction processes.
2. Establish hypoxic co-culture models of GBM cells and CAR-T cells to simulate the tumor microenvironment.
3. Maintain detailed laboratory notebooks and assist in compiling data for reports and presentations on the experimental findings.
2. Establish hypoxic co-culture models of GBM cells and CAR-T cells to simulate the tumor microenvironment.
3. Maintain detailed laboratory notebooks and assist in compiling data for reports and presentations on the experimental findings.
Applicant's Learning Objectives
1. Gain insights into the biology of glioblastoma multiforme (GBM) and the role of EGFRvIII in tumor progression and therapy.
2. Learn about chimeric antigen receptor (CAR) T cell therapy and the mechanisms of immune checkpoint inhibitors like pembrolizumab.
3. Understand the principles of designing and conducting in vitro experiments to evaluate the efficacy of combination therapies.
4. Enhance teamwork and communication skills by collaborating with peers and mentors, and participating in discussions and presentations of research findings.
2. Learn about chimeric antigen receptor (CAR) T cell therapy and the mechanisms of immune checkpoint inhibitors like pembrolizumab.
3. Understand the principles of designing and conducting in vitro experiments to evaluate the efficacy of combination therapies.
4. Enhance teamwork and communication skills by collaborating with peers and mentors, and participating in discussions and presentations of research findings.
Complexity of the project
Moderate