Turning head and neck cancer into immune cells: preclinical validation and clinical plan of TrojanDC

Purpose and goal:

Asgard Therapeutics is a spin-off from Lund University developing a gene therapy based on cell reprogramming for cancer treatment. The aim of the project is to advance cancer immunotherapies for head and neck cancer (HNC) treatment by exploring a proprietary cell reprogramming technology TrojanDC. In this project, together with academic and healthcare partners, we validated the preclinical efficacy of TrojanDC in animal models and patient derived HNC cells as well as refined the clinical trial design.

Expected results and effects:

The tumor growth was controlled when treated with TrojanDC alone or in combination with immune-checkpoint inhibitor (ICI) in ICI resistant mouse models which mimics the majority of HNC patients. Ex-vivo evaluation of human HNC primary cells showed that the cancer cells were efficiently reprogrammed in both 2D and 3D organoid cultures and acquired ability to activate tumor-specific T cell response.

The data supports the feasibility of developing TrojanDC for HNC treatment and informs how to position TrojanDC in the clinical and commercial setting. Approach and implementation:

We evaluated the ability of reprogrammed cancer cells to induce anti-tumor immunity in syngeneic mouse models. The reprogrammed cancer cells controlled tumor growth and extend survival in ICI resistant mice. Cell reprogramming has a synergistic effect with ICI treatment. Additionally, primary HNC cells were efficiently reprogrammed in both 2D and 3D culture. Importantly, the reprogrammed primary cancer cells could present exogenous antigens and activate CD8+ killer T cells.