Date-Time: Wednesday 14 February, 2018 at 15:40
Place : Faculty of Science, SB Building SBZ-14
Host : Onur Cizmecioglu
“Thorlab`s Efforts to Develop Nucleic Acid Based Immunotherapeutics Against Cancer,
Autoimmune, Allergy and Infectious Diseases”
By Prof. Dr. Ihsan Gursel
THORLAB, Therapeutic Oligonucleotide Research Laboratory
Department of Molecular Biology and Genetics, Bilkent University
Abstract:
Bacterial DNA contains immunostimulatory CpG motifs that interact with toll-like receptor 9 (TLR9) on immune cells to stimulate the production of cytokines, chemokines and polyreactive immunoglobulins. Synthetic oligodeoxynucleotides (ODNs) containing CpG motifs mimic the activity of bacterial DNA. Recently, several structurally distinct types of CpG ODN were identified that differentially activate human immune cells. These ODNs may be useful as i) standalone immunoprotective agents, ii) vaccine adjuvants, iii) anti-allergens and in the treatment of iv) infectious diseases and v) cancer. Yet persistent and over-exuberant immune activation can have deleterious consequences, such as increasing the host’s susceptibility to autoimmune and/or autoinflammatory diseases. The immunostimulatory activity of CpG DNA can be blocked by DNA containing “G-rich” suppressive motifs derived from telomeric ends and termed as A151. Synthetic suppressive A151 ODN that can down-regulate cellular elements of the immune system have been developed and are being widely studied in preclinical models. These agents although vary in sequence, mechanism of action, and cellular target(s) but share the ability to suppress a plethora of inflammatory responses. However, the short in vivo circulation time of these ODNs due to nuclease attack hampers their clinical performance. Biologically inspired nanocarriers offer inclusion of protein and nucleic acid-based drugs with high encapsulation efficiency and drug loading thereby improving the clinical performance while alleviating pre-mature elimination. The therapeutic potential of these immunostimulatory and immunosuppressive ODNs will be discussed in this presentation.