Immunovo B.V.

GnRH

Description

Therapeutic vaccines are directed against ‘self’ proteins. ‘Self’ proteins as such make poor immunogens and often do not induce antibodies at all. ImmuNovo has found ways around this obstacle.

Therapeutic vaccines are directed against ‘self’ proteins. ‘Self’ proteins as such make poor immunogens and often do not induce antibodies at all. ImmuNovo has found ways around this obstacle. This depends on alteration of the antigen to make it sufficiently ‘non-self’ to induce antibodies, while maintaining sufficient ‘self’ character to induce antibodies with the ability to cross react with the target protein.  One of the first immunogens developed in this way was a GnRH molecule altered into a tandem Dimer molecule with an inserted unnatural d-lysine (k) amino acid; this molecule was called TDK. Nowadays TDKTM is the generic name for the technology to disguise ‘self’ antigens.

Technologie-TDK ™
Therapeutic vaccines are directed against ‘self’ proteins. ‘Self’ proteins as such make poor immunogens and often do not induce antibodies at all. ImmuNovo has found ways around this obstacle. This depends on alteration of the antigen to make it sufficiently ‘non-self’ to induce antibodies, while maintaining sufficient ‘self’ character to induce antibodies with the ability to cross react with the target protein.

One of the first immunogens developed in this way was a GnRH molecule altered into a tandem Dimer molecule with an inserted unnatural d-lysine (k) amino acid; this molecule was called TDK. Nowadays TDKTM is the generic name for the technology to disguise ‘self’ antigens.

Immunogen % responders
Target hormone pEHWSYGLRPG 0 %
GnRH mono pEHWSYGLRPGC-KLH 40 %
GnRH tandem dimer
pEHWSYk*LRPGQHWSYk*LRPGC
|
pEHWSYk*LRPGQHWSYk*LRPGC
KLH
> 98 %

 

The figure shows the effectiveness of altering the structure of the native target to enhance the effectiveness of an immunogen, in this case the hormone GnRH. Under the column “% responders” the percentage of animals that responded to vaccination with the immunogen by mounting an antibody response is shown. Animals will not respond to the natural hormone GnRH as such; by coupling the hormone to the carrier protein like keyhole limpet hemocyanide (KLH), the barrier against ‘self’ is broken but to a limited extent. As a second step the original amino acid sequence was doubled, resulting in a tandem molecule. Dimerising the tandem through chemically linking two identical molecules and inserting the unnatural amino acid d-lysine (k) resulted in an immunogen that proved effectiveness in almost 100% of animals; the anti-self barrier is successfully broken.
In addition to the TDKTM technology the immune response against relatively weak ‘self’ antigens requires maximisation to obtain the desired effect in all individuals treated. In general this requires the application of an extra aid, an adjuvant. An adjuvant improves the immune system’s susceptibility to the trigger of the antigen because it facilitates delivery, recognition and processing of the antigen.
ImmuNovo has extensive experience with respect to adjuvant technology. This enables it to both select the most suitable commercially available adjuvant for each vaccine program and determine the appropriate dose to be administered leading to response rates in excess of 90%.

Technologie-Trunc ™
Growth factors represent a large group of polypeptides that share the property of inducing cell multiplication. Although the level of sequence similarity between growth factors is low, they can be classified into subfamilies based on their structural and functional similarities. A number of these subfamilies share the common feature that they contain the cys-knot three-dimensional structure.

The cys-knot three-dimensional structure is formed by the arrangement of six cysteines which, through their disulfide bonds form a knot. This cys-knot folding leads to the formation of three distinct domains with two peptide loops protruding from one side of the knot and a single peptide loop from the other side of the knot. These loops are the targets for antibody binding but since they contain discontinuous binding sites until recently only the complete target protein could be used to generate immunogens.

One of the latest developments within ImmuNovo involves the TRUNCTM technology, a further development of CLIPS™. This technology enables reconstruction of discontinuous binding sites on proteins. The technology has been successfully used to reconstruct the binding site of an existing therapeutic monoclonal antibody on VEGF. The reconstructed binding sites themselves can be used as immunogens. This new technique opens the road to a vast number of potential targets within the growth factor subfamilies.

c81e728d9d4c2f636f067f89cc14862c
eccbc87e4b5ce2fe28308fd9f2a7baf3

Details

  • Date April 1, 2015
  • Tags Product
Back to Top