Adoptive therapy with T cell receptor (TCR)-engineered T cells has demonstrated objective responses in multiple types of tumors, including hard-to-treat solid tumors. To further advance adoptive T cell therapy, it is imperative to counteract deficits in immune control, such as limited entrance into tumor tissue, recognition of target antigens and/or effector functions of T cells, that ultimately give way to tumor recurrence. In certain tumors, such shortcomings in local CD8 T cell immunity are a consequence of an intra-tumoral abundance of immune suppressive myeloid cells.
In our laboratory, we have designed and tested engineering strategies to make T cells resistant against local immune suppression. In this project, we welcome you as a PhD candidate to extend such strategies to make T cells resist immune suppressive actions of myeloid cells. To this end, you will make use of advanced in vitro co-culture systems with T cells and myeloid cell subsets, as well as the CRIPR-Cas technology to find candidates for T cell engineering. Subsequently, these new T cell engineering is tested in vivo, and translated into a system that becomes 'switched-on' in the tumor tissue. This project will start in breast cancer models, but will be extended to models of multiple tumor types.
The outcomes are expected to impact adoptive T cell therapy and not only enable targeting of tumor antigens, but also provide resistance in a controlled manner to the immune evasive nature of tumors.
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