Angelica Loskog's research projects on immunostimulatory gene therapy for cancer

The immune system can recognize and kill tumour cells in a similar manner as it recognizes and kills virally infected cells. However, the tumour cells can hide from the immune system as they may downregulate receptors that are needed for immune cell recognition. Further, they may upregulate anti-apoptotic molecules and downregulate death receptors to become resistant to killing.

The tumour microenvironment is immunosuppressed as the tumour release substances that directly inhibit immune cells or attract immunosuppressive immune cells. Hence, even if the immune system is trying to defend us from cancer, it will ultimately fail. We want to change that by re-engineering the tumour microenvironment to become immunostimulatory with gene therapy.

Generating anti-tumour immune responses

Immunostimulatory gene therapy for cancer aims to genetically engineer the tumour microenvironment to generate and support anti-tumour immune responses. In our research group we are inventing novel immunostimulatory gene therapies, performing preclinical evaluation to understand mechanisms-of-action and to demonstrate proof-of-concept, and then evaluating clinical lead products in national or international clinical trials in collaboration with biotech companies, or in academic settings.

We are using two adenoviral platforms to develop our gene therapies. The first product reaching clinical evaluation was AdCD40L, a replication deficient adenovirus. The second product was LOAd703, an “oncolytic” replication competent adenovirus. We have also developed third generation CAR T cells and tested them clinically as the first centre in Europe and now we are interested to understand if immunostimulatory gene therapy can potentiate CAR, TIL or NK cell therapy.