Researchers identify the virus as a promising tool to combat the cancer that affects many people and remains the most difficult skin tumour to treat. The findings can improve the outcome for the patients with melanoma metastases who currently have a poor prognosis.

Globally, melanoma accounts for 4% cases of all skin cancers that have a poor prognosis and low survival rate, while in Russia its share reaches 12.3%. This type of tumour is very aggressive, often insusceptible to chemotherapy, and has a modest sensitivity to immunotherapy. Despite the efforts of the medical community, the 5-year survival rate of the patients with metastatic melanoma still remains between 10% and 15%. However, certain viruses called oncolytic viruses, have been shown to significantly improve the prognosis. Sechenov University scientists and their collaborators have studied the effect of the attenuated Russian vaccine strain of measles virus ‘Leningrad-16’ (L-16) and found that it could be used in the treatment of melanoma. The results have been published in the journal Viruses.

The researchers used a broad range of molecular biology, biochemistry, and cell biology techniques, as well as animal experiments. To test the effect of the L-16 virus in vitro, they employed metastatic melanoma cell lines derived from patients. The cytopathic effects were visible 48–72 hours post-infection. It means that the melanoma cells infected with L-16 did not survive long, whereas the virus did not affect the normal growth of the control cell type. It led to the conclusion that L-16 had a definite preference for the melanoma cells. At the same time, the scientists found that such cells expressed CD46, a protein which acts as a receptor for attenuated strains of measles virus and is normally found on the surface of tumour cells, while CD46 was almost completely absent on the control cells — human dermal immortalised fibroblasts.

Most interestingly, a similar anti-tumour activity was shown in animal models. For this purpose, Balb/c nu/nu female mice were injected subcutaneously with metastatic melanoma cells, and they developed tumours in the flanks. The animals received 3 doses of L-16 with a one-week interval, which resulted in tumour inhibition by 78% on day 56 post-treatment.

The authors conclude that they have established the efficacy and safety of the ‘Leningrad-16’ measles virus in vitro and in vivo. They hope their data could stimulate the development of metastatic melanoma treatment, and the L-16 strain of oncolytic measles virus could serve as a starting point for future improvement by genetic manipulations.

The projected was executed by the scientists from Sechenov University in co-operation with Mechnikov Research Institute for Vaccines and Sera (Moscow), Blokhin National Medical Research Centre of Oncology (Moscow), Togliatti State University (Togliatti, Russia), RUDN University (Moscow), and Engelhardt Institute of Molecular Biology, Russian Academy of Sciences (Moscow).

Read more: Ammour Y, Ryabaya O, Shchetinina Y, Prokofeva E, Gavrilova M, Khochenkov D, Vorobyev D, Faizuloev E, Shohin I, Zverev VV, Svitich O, Nasedkina T. The Susceptibility of Human Melanoma Cells to Infection with the Leningrad-16 Vaccine Strain of Measles Virus. Viruses (2020).

Photo credit: Darko Stojanovic, Pixabay 563423