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

• 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