Around
600 young and senior delegates from 5 continents were in Geneva at
the end of August, for the 11th biennial Congress of the European Association for Clinical Pharmacology and Therapeutics (EACPT).
See below blogs by international delegates on sessions at the 2013 EACPT Congress in Geneva. |
| Jet d'eau - Geneva |
the end of August, for the 11th biennial Congress of the European Association for Clinical Pharmacology and Therapeutics (EACPT).
Laura
Wilkins, University of Warwick, UK
Professor Gunther
Hartmann on Oligonucleotide-based Immunotherapy: On the first evening of the 11th EACPT
congress in Geneva, Professor Hartmann (Head of the BONFOR research committee
at the University of Bonn) introduced congress participants to the world of
oligonucleotide-based immunotherapy.
In simple terms, oligonucleotides are short,
single-stranded nucleic acid (DNA/RNA) molecules. These synthetic molecules are
synthesized to interact specifically, depending on their nucleotide sequence,
with complementary nucleotide sequences found in the body.
Antiviral defence in humans relies heavily on the
detection of the nucleic acids of invading viruses by Toll-like receptors
(TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). Having
worked in the field of oligonucleotides since 1995, Gunther Hartman’s research
has focused on the immunorecognition of synthetic nucleic acids.
In particular, the group discovered that short
interfering RNA molecules (siRNAs) are recognised by TLRs in the human immune
system. The activation of TLR7 was shown to activate the pathway for production
of interleukin 1 beta, initiating an immune response.
The group’s research then focused on the understanding
of RLR mechanisms, these receptors being found in the cytoplasm of all human cells.
Two RLRs (RIG-I and MDA-5) induce an innate immune response when stimulated by
pathogenic RNA. In this way, a synthetic oligonucleotide to activate such a receptor
could serve to stimulate an inactive or deficient immune system, or possibly
even as a vaccine to protect against a particularly virulent virus.
Professor Hartmann’s group worked to characterise
the signalling pathways and the structure of the binding pocket of the
antiviral cytosolic RIG-I, involved in innate response to the influenza virus. This
led to the development of an oligonucleotide mimic of the identified
5’-triphosphate RNA ligand.
This mimic (CpG) is currently undergoing clinical
trials. Interestingly, activation of RIG-I and MDA-5 also caused apoptosis
(programmed cell death) in animal tumour models (in melanoma cells). This
apoptosis was not seen in non-tumour cells, suggesting a use in anti-cancer
therapy.
Professor Hartmann’s lecture showed us that current
research in oligonucleotide-based immunotherapy and even cancer therapy could
still only be just scratching the surface of further possible applications.
More about the 11th EACPT Congress
in Geneva.
