Optimising mRNA vaccines to harness stem-like T cells in cancer

• Applicant: Dr. Hanna Abberger
• Subject Area: Hematology, Oncology ; Immunology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 554758631

The project will focus on “Optimising mRNA vaccines to harness stem-like T cells in cancer”. Current cancer treatment involves the use of immunotherapy such as the inhibition of programmed cell death protein 1 (PD-1) or PD-1 ligand 1 (PD-L1). Immune checkpoint inhibitors reinvigorate T cells from exhaustion and stimulate the immune system to generate terminally-differentiated short-lived effector T cells that eliminate the tumour. However, the efficacy and durability of treatment is limited and varied between cancer type. A subset of CD8+ T cells with stem-like properties (TSL) has come into focus as being essential for successful checkpoint inhibition and positively correlate with disease prognosis. TSL are precursor memory cells that continuously feed the effector T cell pool and are associated with enhanced T cell proliferation as well as T cell persistence. Therefore, we propose that increasing the number of TSL cells in patients will provide an avenue to improve the number of patients that receive benefit from immunotherapy. This project will design and test an mRNA-LNP vaccine strategy to increase the antigen-specific TSL pool. We will establish how this can be used therapeutically in pre-clinical cancer models and determine the mode-of-action. In summary, we hypothesise that modulation of the microenvironment in combination with a lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA (mRNA-LNP) vaccine can boost anti-tumoural immune response.

• DFG Programme: WBP Fellowship
• International Connection: Australia
• Host: Professorin Dr. Joanna Groom