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

Introduction

The aim of this PoC project is to commercialize a new therapy for acute lymphoblastic leukemia (ALL) developed in the 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.

Pre-clinical Validation

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).

Efficacy and Safety Data

In vitro and in vivo data from four different mouse models show:

• Eradication of ALL
• 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.

Clinical Trial

Funding has been secured for an investigator-initiated trial to determine safety and explore the efficacy of TdT-TCR-T-cell therapy – TTT-therapy.

Patient Recruitment

The trial will recruit ALL patients relapsing from/refractory to standard therapy, who have a dismal prognosis and thus a great unmet medical need.

Commercial Development

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.

Team and Strategy

In the proposed ERC PoC project, I and my strong team of advisers with expertise in:

1. Business development
2. Clinical development
3. IPR
4. 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.

Further Research

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.

Medical Need

AML patients have an overall 5-year survival of only 30%, hence a great medical need that potentially could be met by TTT-therapy.

Conclusion

The described work has the potential to contribute to saving lives that would otherwise be lost to acute leukemia.