LOAd – immunostimulatory gene therapy for cancer
LOAd is a group of oncolytic adenoviruses developed by the research group led by Angelica Loskog, Adjunct Professor at Uppsala University.
Oncolytic viruses are genetically modified viruses that infect and selectively multiply inside tumor cells and then burst the cells from within, releasing large amounts of new viruses and substances that can activate the immune system to attack the tumor. These new viruses can in turn infect nearby tumor cells. In addition to their natural cell bursting properties, the LOAd viruses have been equipped with various immune-stimulating genes that activate anti-tumor immune responses. The clinical development of LOAd takes place at the Uppsala-based company Lokon Pharma in close collaboration with Uppsala University and Uppsala University Hospital.
"It has been a very exciting journey to develop a medical product for cancer treatment from the idea stage to assembling the viral genetic vector in the lab and then to treating patients on two continents" says Angelica Loskog.
Patients have been treated with different variants of the LOAd virus in three clinical trials, both in Sweden and in the US. LOKON001 includes patients with pancreatic cancer (Houston), LOKON002 pancreatic and ovarian cancer (Uppsala, Stockholm) and LOKON003 malignant melanoma (Uppsala, Houston and Los Angeles). In Uppsala, patients have been treated at the Blood and Tumor Diseases Phase I unit at Uppsala University Hospital. Gustav Ullenhag, Senior Consultant in Oncology and Professor of Cancer Immunotherapy has been the principal investigator for the studies in Sweden.
Gustav Ullenhag says: "I am passionate about translational immunotherapy research, and the close collaboration between Loskog’s and my research team has made it possible to quickly design and launch clinical studies based on preclinical results. As repeated treatments are given intratumorally and in-patient care is necessary during the first treatments, the studies are particularly challenging to conduct. Good collaboration between investigators, research nurses, radiologists and our in-patient departments has been essential and we have built up a unique expertise."
Patients are treated by varying numbers of intratumoral injections, i.e. the virus is injected directly into the tumor to infect and kill the tumor cells. A total of 37 patients have been treated in the LOKON002 study (completed) at the Phase I unit of Uppsala University Hospital. LOKON003 is still ongoing with several patients under follow-up in Uppsala.
Foto: Ultrasound-guided (percutaneous) injection into the tumor. Photographer: David Magnusson.