Group leader: Mouldy Sioud, DEA Pharm, PhD, Dr Philos
Immunotherapy is based on the generally-accepted hypothesis that the immune system is the best tool humans have for fighting disease. However, despite the advances made in this area, a large proportion of cancer patients showed primary or acquired resistance to current cancer immunotherapies. Most mechanisms driving resistance to therapies are thought to be cancer cell-autonomous, but nonmalignant host cells within the tumor microenvironment could have important roles in both chemo and immunotherapy failure. For example, stromal cells such as macrophages and monocytic myeloid derived suppressor cells express T cell immune checkpoint ligands and immunosuppressive factors such IL-10 and indoleamine 2,3-dioxygenase (IDO), which inhibit T cell responses against tumors. Although co-inhibitory signals expressed by immune cells are important both for the prevention of inappropriate autoimmune responses against self-antigens and termination of normal immune responses once initiated, they represent a huge barrier to the induction of therapeutic anti-cancer immunity. Hence, current therapies should target all these tumor-promoting factors to be effective and result in improved patient outcomes. The principal objective of our work is (i) to develop new targeted antibody- and peptide-based therapies to kill tumor cells and/or immunosuppressive cells, and (ii) to unleash anti-tumor immunity using RNA interference and CRISPR technologies.
Relevant teaching reviews on the topics
- Sioud M (2019).Releasing the immune system brakes using siRNAs enhances cancer immunotherapy. Cancers.11(2). pii: E176. doi: 10.3390/cancers11020176.
- Sioud M (2019). Phage display libraries: from binders to targeted drug delivery and human therapeutics. Mol Biotechnol. 61(4):286-303.
- Sioud M (2018). T-cell cross-reactivity may explain the large variation in how cancer patients respond to checkpoint inhibitors. Scand J Immunol. 87(3). doi: 10.1111/sji.12643.
- Sioud M (2014). Engineering better immunotherapies via RNA interference.Hum Vaccin Immunother. 10(11):3165-74.
- Zins K,Sioud M,Aharinejad S, Lucas T, Abraham D (2015) Modulating the tumor microenvironment with RNA interference as a cancer treatment strategy. Methods Mol Biol. 1218:143-61.
- Sioud M (2009). Does our current understanding of immune tolerance, autoimmunity, and immunosuppressive mechanisms facilitate the design of efficient cancer vaccines? Scand J Immunol. 2009 516-25.
- Sioud M(2006)Innate sensing of self and non-self RNAs by Toll-like receptors. Trends Mol Med.12(4):167-76.