PhD defence A. (Adva) Kochavi

Below is a brief summary of the dissertation:

Cancer cells are constantly adapting to challenging conditions, including cancer treatments and limited availability of amino acids, the building blocks of proteins. To survive this stress, cancer cells can alter the way they produce proteins, sometimes generating abnormal proteins that are not found in healthy cells. This thesis investigates how changes in transfer RNAs (tRNAs)—small molecules that help build proteins—contribute to this process and how these abnormal proteins could be used to target cancer.
By developing a new technology to study tRNAs in cancer cells, we identified how applied stress conditions such as amino acids shortages and chemotherapy reshape tRNA activity. These changes can disrupt accurate protein production, causing cancer cells to make abnormal proteins. Importantly, fragments of these abnormal proteins can be displayed on cancer cells and are recognized by the immune cells as “foreign” signals. We showed that delivering engineered immune cells (TCR T cells) against these “foreign” signals allows targeted elimination of cancer cells in experimental models.
Together, this research reveals that cancer cells’ ability to adapt their protein production machinery can become a weakness. By understanding and exploiting these stress-induced changes, we uncover new opportunities to develop personalized immunotherapies that help the immune system recognize and attack cancer cells more effectively.