Targeting Acute Leukemia with TdT-TCR-T-cell therapy

ended

The aim of this PoC project is to commercialize new therapy for acute lymphoblastic leukemia (ALL) developed in context of my ERC consolidator grant. T-cell receptors (TCRs) have in recent years emerged as promising therapeutic molecules in cell- and gene-therapy of cancer. I have completed the pre-clinical validation of a TCR that recognizes an HLA-bound peptide from a novel target, the nuclear enzyme terminal deoxynucleotidyl transferase (TdT-TCR). In vitro and in vivo data from four different mouse models show eradication of ALL and no indications of toxicity. T-cells genetically modified with the TdT-TCR effectively kill lymphoblastic cancer cells while sparing healthy B and T-cells, myeloid cells and hematopoietic stem cells. Funding has been secured for an investigator-initiated trial to determine safety and explore efficacy of TdT-TCR-T-cell therapy – TTT-therapy. The trial will recruit ALL patients relapsing from/refractory to standard therapy, who have a dismal prognosis and thus a great unmet medical need. To facilitate commercial development, I have created a start-up company and secured the company exclusive licenses for the patents on the TdT-TCR and the technology used for the development, on which I am the main inventor. In the proposed ERC PoC project, I and my strong team of advisers with expertise in the business development, clinical development, IPR and financial aspects needed for commercialization, will conduct a market analysis for TTT-therapy and develop an IPR and business strategy for the start-up company. Since several studies report expression of TdT in acute myeloid leukemia (AML), I will conduct laboratory research to determine if the TdT-TCR can also mediate killing of AML cells. AML patients have an overall 5-year survival of only 30% and hence a great medical need that potentially could be met by TTT-therapy. The described work has the potential to contribute to saving lives that would otherwise be lost to acute leukemia.