Preclinical and clinical studies of cell therapy for patients with therapy resistant melanoma

Melanoma occurs when pigment cells, melanocytes, acquire oncogenic mutations and they start to divide uncontrollably. If the cells spread and form metastases then melanoma is potentially a deadly disease.

The last few years have seen a revolution in the treatment of metastatic skin melanoma, predominantly with the introduction of immune checkpoint inhibitors (ICIs).

Unfortunately, half of all patients’ melanoma are resistant, or acquire resistance, to ICIs, resulting in death of over 500 Swedes every year.We have shown in animal models that cell therapy is a possible way to treat therapy resistant melanoma.

We have now established the capability and have approval to start a first clinical trial on cell therapy and we will start a second trial within the grant period.

We will also in parallel conduct a host of discovery experiments on biopsies from patients and use our generated patient-derived xenograft (PDX) mouse models to optimize TIL products for therapy.

We will also use an automated pipeline for generating lipid nanoparticle (LNPs) that carry modulating mRNAs designed to stimulate cell therapy. Finally, we will develop novel CAR-T cell products based on our discovery pipeline.

This includes using CRISPR engineering to knockin CAR constructs into loci that will disrupt autologous recognition of the engineered T cells. All cell products will be tested in PDX models and in companion dogs before human phase 1 clinical trials.