The Luxembourg Institute of Health (LIH) and the renowned German Cancer Research Centre (DKFZ) have inaugurated a new binational research unit named LOVIT – „Laboratory of Oncolytic Virus Immuno-Therapeutics” – in the presence of the directors of the two institutes. This unit will develop new innovative strategies to fight cancer in the recently emerged field of oncolytic virotherapy, a treatment that uses viruses to destroy cancer cells.
The new research unit LOVIT was created following the signing of an agreement between the two institutes in December 2016. Jointly funded. It is in addition supported by a generous grant from the Luxembourg Cancer Foundation “Fondation Cancer”. Dr Antonio Marchini, an Italian scientist who has been very active over the last ten years in the field of virotherapy to fight cancer, will direct the unit. His team, which will be composed of about eight members, will work in laboratory space of LIH’s Department of Oncology in Luxembourg City and at the premises of DKFZ in Heidelberg.
Viruses as promising anticancer therapy
Oncolytic virotherapy for cancer is a treatment based on viruses that preferentially infect cancer cells, multiply inside them and kill them by lysis, meaning by making them “burst”. Oncolytic viruses are promising anticancer agents because they selectively kill cancer cells and elicit on top a robust anticancer immune response that stimulates the body to fight cancer.
Recently, the first oncolytic virus was approved for treatment of metastatic skin cancer by the Food and Drug Administration in the United States and the European Medicines Agency in Europe. Following this breaktrough, oncolytic virotherapy is gaining momentum quickly, with a number of oncolytic viruses being tested in clinical trials for the treatment of different tumors.
One oncolytic virus is the parvovirus H1-PV, which normally infects rats and does not cause disease in humans. It is one of the smallest viruses in nature and can be considered as a “smart nanoparticle” with a natural propensity for targeting human cancer cells. Dr Marchini explains its action: ‘Like a parasite, this virus multiplies in cancer cells taking advantage of the cells’ functions. After its multiplication, the virus – just as an intelligent ticking-time bomb – triggers the destruction of the cancer cell. Viral particles are then released in the near surroundings, enter and multiply in other cancer cells, and finally dissemiate thorough the whole tumour. Importantly, healthy cells are not harmed in this process.’
A next generation of viruses
At DKFZ, Dr Marchini and co-workers developed a first generation of engineered viruses endowed with enhanced anticancer activity. They introduced the DNA (genetic information) of the H1-PV parvovirus into another virus, commonly used in vaccines, the adenovirus, to generate a so-called chimera. It is a Trojan horse strategy in which the adenovirus (the Trojan horse) is used as a shuttle to bring the parvovirus DNA into cancer cells. Parvovirus particles (the soldiers in this comparison) are then produced and released outside ready to infect and kill other cancer cells.
At LOVIT, the chimeric viruses will be further developed. They also allow for introducing additional therapeutic genes that could help to further boost the body’s immune reponse. The experiments with the chimeras will first need to be confirmed in preclincal studies in animal models. Dr Marchini hopes that a first clinical trial with patients could be launched in about five years. ‘Virotherapy has potential to be used as well in combination with other treatments to generate synergistic anticancer effects’, explains Dr Marchini. ‘It would be thrilling to test our new viruses in combination with chemo-, radio- and immunotherapy.’
Providing therapeutic options for different cancer types
LOVIT, integrated into LIH’s Department of Oncology, will closely collaborate with the other research units of the department, in particular with the NorLux Neuro-Oncology Laboratory working on brain tumours. ‘At the beginning’ – tells Dr Marchini – ‘together with our collaborators at LIH and DKFZ we will target brain tumours and pancreatic cancer which are among the most fatal cancer types still in need for effective therapies. In the future we plan to extend our research to lung cancers. Our aim is to establish additional collaborations inside and outside Luxembourg for the sake of expediting cancer research and making the patients benefit from new discoveries. We will work hard and to our best with the hope to provide cancer patients new treatment options.’
‘Cancer research in Luxembourg has reached a high scientific level in the last years, allowing us to undergo collaborations with recognised institutes such as DKFZ’, points out Dr Catherine Larue, CEO ad interim of LIH. ‘With the creation of LOVIT we will be able to investigate new therapeutic paths that are very promising for the patients.’
Photo: © Dr Antonio Marchini/ LIH