Therapeutic Exploration of ydT cells

Summary

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Despite significant efforts to improve treatments, many types of cancer remain incurable. Patients often undergo multiple forms of treatment, such as surgery, radiation, or chemotherapy. These treatments can cause considerable stress, pain, and adverse side effects, which can greatly reduce quality of life. For this reason, researchers are not only focused on improving existing therapies but are also exploring novel approaches. One promising new direction lies within our own bodies: the immune system, which protects us daily from a wide range of diseases. Increasingly, research is directed toward harnessing the immune system to fight cancer, particularly through the use of T cells.

In this thesis, we have investigated a special type of T cell: the γδT cell. We exploited various strategies to improve current γδT cell-based therapies and demonstrated the unique therapeutic potential of γδT cells in two types of solid tumors. First, we explored ways to enhance the efficacy of our γδT cell-based therapies in the form of bispecific molecules (GABs), using multiple approaches. One of these strategies also proved to be effective in a different γδT cell-based therapy, TCR-transduced T cells called TEGs. Furthermore, we examined the potential of distinct γδT cell subsets in glioblastoma and proposed strategies to overcome potential tumor escape mechanisms. Lastly, we studied the role of γδT cells in colorectal cancer, which yielded novel insights for future treatment approaches. Altogether, our findings contribute to the broader understanding of γδT cells and offer new opportunities for improving existing therapies and developing innovative immunotherapeutic strategies against cancer.

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