Novel human suicide gene for oncolytic virotherapy and safety switch in cell based therapies

CONECTUS ALSACE



28 Juillet 2015

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Fields

Biology / Medical

Sectors

Health
  • Based on a novel approach of gene evolution (Retrovolution) unprecedented highly potent hdCK mutants were isolated
  • hdcK M36 mutant results in only 4 mutations compared to the WT hdCK but exhibits, on Gemcitabine resistant cells (Messa-10K) a 900-fold decrease in IC50 with Gemcitabine and 10 000-fold decrease with Cytarabine

TECHNOLOGY

  • A first mutant G12, already showed promising results (published). By evolving the G12 gene, another even more potent mutant (M36) was selected and tested on Messa 10K cells
  • M36 induces unprecedented 900 fold decreasein IC50 for Gemcitabine and 10000 fold for cYTARABINE
  • Mutation results in loss of affinity for the natural substrate

APPLICATION

  • Suicide Gene therapy for anti-cancer treatment
  • Safety switch for cellular therapy approaches in cancer and regenerative medicine (transplantation, CARs or TCRs, iPSC based therapies)

INNOVATION ADVANTAGES

  • Inducing cell death in presence of low doses of cytotoxic dru g
  • Currently clinically employed anticancer drug
  • Countering the unwanted side-effects and improving the effectiveness
  • Overcoming potential resistance arising during treatment
  • Human enzyme mutant : Absence of Immunogenicity
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