Group leader:  Mouldy Sioud, DEA Pharm, PhD, Dr Philos

Immunotherapy represents a promising approach to cancer treatment. However, in many cancers this form of therapy has remained largely ineffective. There are still major challenges that need to be addressed such as the presence of a powerful immunosuppressive environment in solid tumors, loss of tumor antigen expression, and downregulation of MHC class I molecules at the surface of cancer cells. Among the innate immune cells recruited to the tumor site, macrophages are particularly abundant and are involved in tumor growth, angiogenesis, metastasis and resistant to current therapies. Hence, new platforms for antibody and target discovery are needed to expand immunotherapy options for cancer patients with limited treatment alternatives. A novel immunotherapy that simultaneously target tumor cells and macrophages would have significant clinical impact for various types of cancer. The current research activity in our group is focusing on the development of new antibodies and peptides targeting receptors/proteins expressed on the cell surface of cancer cells or macrophages for use in cancer immunotherapy and diagnosis.
Below are some previous and new key achievements:

• Archaebacterial topoisomerase II shares both prokaryotic and eukaryotic features. Relevant to evolution, pointing to a common ancestor for the animal and archaebacterial topoisomerases (Sioud et al.,  Eur. J. Biochem 1987; Nucleic Acids Res 1987, 1988; Biochemistry, 1989, and more).
• Phage-display as a new platform for fingerprinting the circulating antibody repertoire: Relevant to biomarkers and mimotope discovery (Sioud et al., Eur. J. Immunol. 1993; Ann. Rheum. Dis 1996; Mol. Med 2001; Eur. J. Immunol. 2002 and more).
• Involvement of cellular proteins in ribozyme (an RNA enzyme) activity in mammalian cells.  Relevant to the interplay between proteins and RNA catalysis (Sioud M, J. Mol. Biol 1994; Nucleic Acids Res 1994; J. Mol. Biol. 1996;  Eur. J. Immunol. 1996; Nature Biotechnology 1998, and more).
• A new experimental approach for the identification of antisense transcripts in mammalian cells. Relevant to gene regulation by non-coding RNAs (Røsok and Sioud, Nature Biotechnology, 2004; Discovery. Med, 2004, and more).
• RNA chemical modifications evade the recognition by the immune system: Relevant to therapeutic RNAs and mRNA vaccine design to avoid unwanted immune responses (Sioud M, J. Mol. Biol. 2005; Expert Opin Drug Deliv 2005; Eur. J. Immunol. 2006; Trends Mol. Med. 2006, and more).
• Human hematopoietic stem cells sense microbes via Toll-like and NOD receptors: Relevant to the regulation of hematopoiesis during infection and host-microbe interactions (Sioud et al.,  J. Mol. Biol. 2006; Eur. J. Immunol. 2007;  J. Leukoc. Biol. 2009, and more). 
• Development of new human antibodies, antibody-drug conjugates, peptide-Fc fusion proteins, and lytic peptides for targeting tumor cells and/or macrophages. Relevant to cancer immunotherapy (Sioud M et al.,  Molecular Therapy-MCD, 2015; FASEB J, 2018; Cancers, 2019, 2021, and more).