Vincenzo Cerullo started in the beginning of September 2012 as a Group Leader in the CDR and newest tenure track associate professor in the Faculty of Pharmacy. He focuses on personalized drugs – drugs that work only for a specific tumour of a specific type of patient. This is accomplished through using specialized viruses. It all started during his years in the U.S.A. Dr. Cerullo worked in the Department of Human and Molecular Genetics in the Baylor College of Medicine, USA. Here, researchers investigate how to replace defective genes by using helper-dependent adenoviruses.
In these helper-dependent adenoviral vectors, the virus genome is first depleted of all viral genes. Then, the functional human gene is replaced in the viral genome. The virus enters the cell and releases the gene inside, thereby supplying the cells with functional copies of the appropriate gene. In the best case, the virally infected cells can express that gene perpetually. One of the great advantages of this system is that the the gene does not integrate into the host cell’s genome. Because of this, there is no risk for insertional mutagenesis, where the original DNA could change because of the inserted
and integrated repair gene. This approach has the potential of solving various monogenic diseases with a single dose.
The immune system kicks in
The only problem with helper-dependent adenoviral vectors is that the amounts of the adenoviruses injected to the blood stream need to be very high to achieve a therapeutic dose. That level of virus in the blood stream invariably activates the immune system, and this can cause problems in treatment. In Dr. Cerullo's work, activation of the immune system seemed an unfortunate and persistent consequences of viral therapy. However, he gradually came to understand that he could use oncolytic viruses not only to selectively kill cancer cells, but also to activate the immune system. The virus is, after all, eliminated quite fast by the immune system. The long-term goal of the group is to find a way to disguise the virus as a tumor, so that one could divert the immune system towards it.
Selected Publications:
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Immunological effects of low-dose cyclophosphamide in cancer patients treated with oncolytic adenovirus. Cerullo V., Diaconu I., Kangasniemi L., Rajecki M., Escutenaire S., Koski A., Romano V., Rouvinen N., Tuuminen T., Laasonen L., Partanen K., Kauppinen S., Joensuu T., Oksanen M., Holm S.L., Haavisto E., Karioja-Kallio A., Kanerva A., Pesonen S., Arstila P.T., and Hemminki A. Molecular Therapeutics. 2011. Sep;19(9):1737-46.
Oncolytic adenovirus coding for granulocyte macrophage colony-stimulating factor induces antitumoral immunity in cancer patients. Cerullo V., Pesonen S., Diaconu I., Escutenaire S., Arstila P.T., Ugolini M., Nokisalmi P., Raki M., Laasonen L., Särkioja M., Rajecki M., Kangasniemi L., Guse K., Helminen A., Ahtiainen L., Ristimäki A., Räisänen-Sokolowski A., Haavisto E., Oksanen M., Karli E., Karioja-Kallio A., Holm S.L., Kouri M., Joensuu T., Kanerva A., and Hemminki A. Cancer Research. 2010. Jun 1;70(11):4297-309.
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