Our Tetanus-Epitope Targeting-platform (TET-platform™) is created on a unique, patented tetanus toxin-derived strategy that protects the peptide drug from degradation and facilitates both drug uptake and activation of the cellular immune response.
The same immune cells that take up the peptide drug also receive an immune activating signal to combat the cancer towards which the drug is designed. This platform is used to create the next generation of synthetic peptide cancer vaccines, and can be used for multiple indications.
The TET-platform is based on a patented B cell epitope derived from tetanus toxoid, MTTE (Minimal Tetanus Toxoid Epitope), coupled to tumor-derived T cell epitopes (i.e. epitopes that are specific for the cancer in question) via a core molecule. In the case of our TENDU-1 vaccine, tumor derived epitopes come in the form of synthetic long peptides harboring multiple T cell epitopes (see Pipeline).
The tetanus toxoid antibodies that people have in the body after vaccination will be attracted to the MTTE part of our vaccine molecule and form an immune complex that will work as an adjuvant, or immune system enhancer. This aids efficient drug antigen delivery to, and further maturation of, dendritic cells (DCs) – the cells in the body that that are crucially involved in de novo T cell priming. T cells are potent anti-tumor responders. The TET adjuvant will work much like a ‘targeted robot’ in delivering the cancer specific vaccine to the DCs.
The ultimate goal with this design is to ensure that the drug antigen is delivered to the same antigen-presenting cells (APCs) that are also activated by the tetanus immune-complex, i.e. we deliver a unique adjuvant and drug in one, a unique composition that aids the therapy’s efficacy.
When the entire vaccine complex is taken up by the DCs in the body, it is degraded and cleaved into short peptide sequences. This enables the DC to expose the short peptide sequences and present them (as epitopes) to T cells; the latter subsequently killing the tumor cells as well as attracting immune cells to the tumor site.
The MTTE-part of the complex can be linked to any immune targeting therapeutic molecule, making the TET-approach a truly generic platform to be exploited by us and/or potential partners, and offers improved drug efficacy through linking strategies.
We currently have one product in pipeline, the TENDU-1 a prostate cancer-specific drug vaccine candidate. It is an innovative vaccine mix, with the Minimal Tetanus Toxoid Epitope (MTTE) conjugated to long synthetic peptides, harboring multiple prostate-specific tumor-associated epitopes. This strategy ensures that the vaccine is delivered as an antigen-antibody immune complex formula.
Our goal is to ensure that the peptide drug is delivered to the same immune cell that is also activated by the drug immune-complex. To achieve this, we make use of the fact that humans are, or easily can be, vaccinated against tetanus, and thereby have tetanus toxoid antibodies circulating in the body.
Linking T cell epitopes to a common linear B cell epitope: A targeting and adjuvant strategy to improve T cell responses. Mangsbo S.M. et al. Molecular Immunology, 2017
Circulating specific antibodies enhance systemic cross-priming by delivery of complexed antigen to dendritic cells in vivo. van Montfoort N. et al. European Journal of Immunology, 2012
Antigen storage compartments in mature dendritic cells facilitate prolonged cytotoxic T lymphocyte cross-priming capacity. van Montfoort N. et al PNAS, 2009
Complement activation by CpG in a human whole blood loop system: mechanisms and immuno-modulatory effects. Mangsbo S.M. et al. Immunology, 2009