Research Directions
Immune checkpoint blockade (ICB) and CAR-T cell therapy have already transformed the treatment landscape for certain cancers, such as melanoma, lung cancer, and B-cell malignancies, providing patients with new options superior to conventional therapies. ICB works by blocking inhibitory signals such as PD-1/PD-L1 or CTLA-4 to restore the function of exhausted T cells, whereas CAR-T cells are genetically engineered to express tumor-specific receptors, enabling direct cytotoxic activity against tumor cells. Nevertheless, these therapies still face significant challenges. ICB has limited response rates in so-called “cold tumors” with low immunogenicity and is often accompanied by immune-related adverse events. Although CAR-T has achieved remarkable success in hematologic malignancies, its application in solid tumors remains constrained by the immunosuppressive tumor microenvironment, antigen heterogeneity, and insufficient persistence of infused cells.
These limitations have driven research toward next-generation cell therapies, including unconventional lymphocyte populations such as γδ T cells and natural killer (NK) cells, as well as engineered platforms such as CAR-NK and CAR-γδ. These strategies can recognize tumors through MHC-independent mechanisms, have a lower risk of allogeneic immune rejection, and hold promise for development as off-the-shelf cancer immunotherapies.
To explore the potential of next-generation cell therapies, our unit is dedicated to developing γδ T cells, which possess both innate and adaptive immune functions.
We plan to address the issue from three perspectives:
- Develop and optimize methodologies for the ex vivo expansion of γδ T cells.
- Use CRISPR/Cas9 for high-throughput genome-wide screening to identify editable gene modules.
- Through collaboration with Chang Gung Memorial Hospital, attempt to isolate highly specific anti-tumor γδ TCRs from cancer patients as a therapeutic option for TCR-T cell therapy.