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The role of protein sulfation in CD8+ T cells

The role of protein sulfation in CD8+ T cells

Klaus Schmetterer (ORCID: 0000-0001-9328-4871)
  • Grant DOI 10.55776/PAT7770724
  • Funding program Principal Investigator Projects
  • Status ongoing
  • Start November 11, 2024
  • End May 10, 2028
  • Funding amount € 599,998
  • Project website

Disciplines

Medical-Theoretical Sciences, Pharmacy (100%)

Keywords

    CRISPR genome engineering, Tumor Immunology, CD8+ T cells, Protein Sulfation, Post Translational Modification

Abstract

Our immune system is our body`s natural defense against diseases, including cancer. CD8+ T cells, a type of white blood cell, play a crucial role in this defense. They can recognize and eliminate cancer cells, making them a powerful tool in cancer treatment. However, cancer cells often find ways to evade or suppress T cells, limiting the effectiveness of our immune response. In recent years, scientists have developed innovative cancer treatments called immunotherapies, which aim to boost our immune system`s ability to fight cancer. One promising approach is CAR T cell therapy, where a patient`s own T cells are genetically modified to better target cancer cells. While this therapy has shown remarkable success in some blood cancers, it often falls short in treating solid tumors. Our research project aims to enhance the power of T cells for cancer immunotherapy by focusing on a process called protein sulfation. This process involves adding small chemical sulfur groups to proteins in CD8+ T cells, which can affect how these cells function. We have discovered that by manipulating an enzyme called TPST2, which is responsible for protein sulfation, we can make T cells more active and effective at fighting cancer cells. Using cutting-edge gene editing techniques (the CRISPR/Cas9 system), we plan to identify specific TPST2 target proteins in T cells that are responsible for this effect and thus can boost the cancer-fighting abilities. We will test these enhanced T cells both in laboratory experiments and in animal models to ensure they are safe and effective. Our goal is to develop new strategies to create more powerful CAR T cells that can overcome the challenges of treating solid tumors. This research could lead to more effective cancer immunotherapies, potentially offering new hope to patients with difficult-to-treat cancers. By unraveling a yet uncharted topic of T cell biology and harnessing the power of gene editing, we aim to push the boundaries of cancer treatment and contribute to the ongoing revolution in immunotherapy.

Research institution(s)
  • Medizinische Universität Wien - 100%
Project participants
  • Ralf Schmidt, Medizinische Universität Wien , national collaboration partner
  • Robert Kralovics, Medizinische Universität Wien , national collaboration partner

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