Research projects

Immune checkpoints are regulatory mechanisms that prevent excessive or inappropriate immune responses. However, tumor cells can exploit these mechanisms to evade the immune system’s response. One of the most studied immune checkpoint mechanisms in cancer is the PD-1/PD-L1 axis. In this process, tumor-associated macrophages and tumor cells can express PD-L1, a protein that binds to the PD-1 receptor on T cells. This interaction reduces the ability of CD8+ T cells to attack the tumor, weakening the immune response. Blocking the PD-1/PD-L1 axis is crucial to reversing this suppression.

Immunotherapy with modified T cells (CAR-T) targeting PD-L1 has shown efficacy in certain types of cancer but faces challenges in solid tumors. These challenges are related to the immunosuppressive tumor microenvironment and antigenic evasion, such as changes in the expression of glycans (sugar molecules) on the cell surface. In particular, sialic acids, key components of glycans in tumor cells, interact with Siglec receptors on immune cells infiltrating the tumor, modulating their function and promoting cancer progression.

To counteract this tumor immune evasion strategy, we propose an innovative solution: developing a multi-specific CAR-T cell capable of simultaneously targeting PDL1 and Siglecs. This approach will enhance the immune response within the tumor microenvironment, especially in solid tumors, where more effective therapies are needed. Our project involves modifying anti-PD-L1 CAR-T cells through metabolic labeling, incorporating specific glycans targeting Siglecs. These modified cells will be evaluated in in vitro cell models to validate their efficacy.

This strategy has the potential to overcome current challenges in the treatment of solid tumors, driving the development of more effective and precisely targeted immunotherapies.