This project aims at assessing single T cell reactivity by a combinatorial approach where all T cell from a sample (tumor infiltrating T cells) are placed in contact with one of the APC out the patient specific cell library transduced to express relevant neo-antigens. Early signs of T-cell activation will be optically measured by tracking the rapid increase of intracellular Ca2+ concentration following the T cell receptor (TCR). For this purpose, we will develop a droplet microfluidics platform that will combine high speed and high yield cell pairing in single droplet, optimize the cell-cell contact by appropriate in-droplet flow recirculation and fast sorting based on calcium imaging.
Immunotherapy holds great promise and potential for cancer treatment and many trials are under way. Unfortunately, even if successful, routine clinical use remains impossible today. Identification of suitable tumor antigens is very time consuming and resource intense which limits the use of cell-based Immunotherapy in clinical practice. The scope of this project is to develop high-throughput methods for fast identification of suitable target antigens and “production” of tumor-destroying immune cells.
