Immunostimulatory gene therapy has been evaluated for patients with malignant melanoma
A new clinical study shows promising results from treatment with immunostimulatory gene therapy in combination with checkpoint inhibitors for patients with malignant melanoma. The study has been published in the scientific journal Nature Communications.
LOAd703 is administered by injection into the tumour. Tumour-targeted T cells are activated and can attack and kill tumour cells.
The first line therapy for patients with metastatic malignant melanoma is usually treatment with protein kinase inhibitors or antibodies that block PD-1/PD-L1 signalling, known as checkpoint inhibitors, often in combination with other therapeutic antibodies. Unfortunately, for patients who do not respond to treatment initially, or who become resistant over time, there are not many effective treatment options.
In the new study, the researchers tested treatment with the immunostimulatory virus LOAd703 together with a PD-L1 blocking antibody for patients who had previously become refractory to PD-1/PD-L1 blockade.
“LOAd703 is a modified virus that contains two human immunostimulatory genes. The virus is designed to induce inflammation in the tumour and drive the expansion of tumour-targeted T cells inside the body, which can subsequently destroy the tumour. This allows LOAd703 to re-sensitise patients to a new round of checkpoint treatment”, says Angelica Loskog, whose research group at IGP has developed LOAd703.
In the current study, researchers found that disease control could be demonstrated in more than half of the patients and that two-year survival was 57 per cent.
Particularly promising results were that for the lower dose level tested, survival without disease progression was 9.7 months and median survival was 26.3 months. By comparison, median survival is approximately 6 months in similar patients treated with cytostatic drugs, as shown in previously published meta-analyses.
The study also presents biomarker data analysed at IGP, which confirmed LOAd703’s immunostimulatory function in patients.
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LOAd703 is being developed for clinical use in collaboration with the Uppsala-based company Lokon Pharma.
The clinical study was sponsored by Lokon and conducted at Uppsala University Hospital by Gustav Ullenhag and doctoral student Viktoria Ekström-Ryden, in collaboration with clinics in the United States: The Angeles Clinic and Research Institute, a Cedars Sinai Affiliate, and Baylor College of Medicine.