Oncolytic Coxsackievirus Variante PD for Treatment of Cancer

Immunotherapies using oncolytic viruses offer a novel specific possibility of treating malignant tumors. Coxsackievirus B3 (CVB3) as an oncolytic RNA-virus possesses particular benefits including a short replication cycle, the generation of an abundant number of virus progeny, a strong cytolytic activity, and the introduction of robust anti-cancer immune responses. However, it was shown that the wild type CVB3 (Nancy strain) can cause severe inflammations and infections in humans and therefore an application as a safe oncolytic virus is questionable.

The invention presented here uses a modified variant of the CVB3 wild type, isolated after serial passaging in human fetal primary fibroblast cells and chinese hamster ovary cells. The new CVB3–variant (PD-0) shows strong lytic effectiveness in tumor cells and inhibits the tumor growing in vivo without causing side effects. The altered amino acid sequence, positively influencing the absorption of the virus into tumor cells, seems most likely to be responsible therefore. A cDNA clone of PD-0 is available, which makes simple genetic modifications to the virus genome possible. Thus, the invention offers a new, safe method of cancer treatment. Furthermore, PD‑0 represents a basis for the development of novel PD-0-virus variants with further enhanced properties. This opens up the possibility to adapt the used virus more specifically to the tumors, and enhancing the efficiency of the treatment even more.