Thymidylate synthase/poly-epitope peptide vaccine
The invention concerns a peptide having anti-tumour activity, designated TS/PP, and its derivatives. In particular, the invention concerns a peptide with anti-tumour preventive and therapeutic activity, also in combination with other known anti-tumour compounds such as, 5’-fluorouracil.
Thymidylate synthase (TS) is an intracellular enzyme whose expression is controlled by the levels of its co-factors and substrates, and by genes involved in cell cycle, thus being temporally expressed only during the S phase. By contrast, TS is constitutively expressed in tumour cells. Once metabolized, the cytotoxic polychemotherapeutic drug 5’-fluorouracil (5’-FU) is able to permanently inhibit the TS enzyme, which is rapidly degraded in the cytoplasm. Nevertheless, adaptative neoplastic cells over-express the TS in response to 5’-FU exposure. The synthetic 28-mer anti-tumour peptide TS/PP was developed for use in immunotherapy. Combined with conventional fluoropyrimidine-based chemotherapy, TS/PP induces polyepitope cytotoxic T-lymphocyte (CTL) response capable of destroying TS over-expressing tumour cells, while simultaneously displaying a preventive immunoprotective activity.
- A method for obtaining TS-activated CTL lines;
- Preventive anti-tumour formulation including a pharmaceutically effective amount of the peptide and appropriate excipients, diluents and/or solubilizing agents;
- Includes a further anti-tumour active ingredient, preferably 5’-FU, but also other chemotherapeutic drugs.
- Induction of polyepitope cytotoxic T-lymphocyte response against TS-overexpressing tumour cells;
- Preventive immunoprotective action;
- Immunological and anti-tumour activity demonstrated in vitro (human cells) and in vivo (transgenic-HHD mice);
- Not associated with onset of any adverse event or autoimmunity.