Herpes viruses – hope for melanoma patients

iStock_000034756166_DoubleMelanoma originates from pigment cells – melanocytes. Melanoma is the main cause of deaths of skin neoplasms. It is one of the most refractory neoplasms. Many scientific reports indicate the possibility of using the virus as a weapon against cancer, especially in inoperable cases.

More and more attention in the treatment of cancer is paid to the “oncolytic viruses”. The term “oncolytic virus” refers to a strain of the virus, which is able to destroy cancer cells while sparing cells that have not undergone neoplastic transformation. The main problem of this therapy is incomplete knowledge about virus’s activity. Therefore the pathogenetic potential in host’s organism is not fully understood. In this case it is necessary to create viruses which have the highest possible clinical activity with minimal pathogenetic potential.

At the turn of 2015/2016 FDA have officially accepted the oncolytic viruses therapy in the treatment of inoperable melanoma of the skin and lymph nodes. The main biologically active component is the human herpes simplex virus 1 (HSV-1), which was attenuated by deleting both copies of US12 and RL1 genes – main virulence factors. Importantly, despite the modification, viruses remained sensitive to essential anti-viral drugs. It creates a possibility of terminating the replication and viral spread beyond the tumor cells.

Effectiveness of the drug was assessed on a group of 436 patients with inoperable metastatic melanoma. They were divided into two groups. First group was using 6-month treatment viruses while the second group received treatment stimulating factor granulocyte-macrophage colony-macrophage (GM-CSF). In the first group 6-months virus therapy was administered, while the second group received granulocyte-macrophage colony stimulating factor (GM-CSF). Therapy efficacy was estimated on the basis of three indicators: the rate of continuous response (DDR) is defined as a permanent response to treatment after at least 6 months, overall survival (OS) and overall response rate (ORR). The effects of the treatment have been very promising. Oncolytic viruses therapy was superior in comparison to the GM-CSF treatment in DDR (16.3% vs. 2.1%), ORR (26.4% vs. 5.7%). The median survival rate was respectively 23.3 months for virus therapy and 18.9 months for GM-CSF. In addition, an innovative therapy proved to have a very favorable safety profile. The most common side effects were fever, fatigue and chills. Moreover, there were no treatment-related deaths. However, taking into account the fact that the medicine contains live viruses, they should not be administered to pregnant women and people with immune deficiencies.

Undoubtedly, this discovery brings great hope for patients with advanced melanoma. Researchers stand face to face with another challenge of assessing the suitability of the treatment for other types of neoplasms. Interesting issue is also combination of the therapy with the currently available methods of treating tumors ie. radiation therapy, chemotherapy, surgical therapy. Therefore, further studies are necessary to solve these intriguing problems.

Written by: Katarzyna Godzisz , Hubert Opaliński, Michał Godzisz

1) Jonathan Pol, Guido Kroemer & Lorenzo Galluzzi (2016) First oncolytic virus approved for melanoma immunotherapy, OncoImmunology, 5:1, e1115641, DOI: 10.1080/2162402X.2015.111564
2) Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov 2015; 14:642–62; PMID:26323545
3) Pol J, Bloy N, Obrist F, Eggermont A, Galon J, Cremer I, Erbs P, Limacher JM, Preville X, Zitvogel L et al. Trial watch: oncolytic viruses for cancer therapy. Oncoimmunology 2014; 3:e28694; PMID:25097804
4) Vacchelli E, Eggermont A, Sautes-Fridman C, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: oncolytic viruses for cancer therapy. Oncoimmunology 2013; 2:e24612; PMID:23894720
5) Liu BL, Robinson M, Han ZQ, Branston RH, English C, Reay P, McGrath Y, Thomas SK, Thornton M, Bullock P et al. ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther 2003; 10:292–303

Would you like to know more? Watch on MEDtube.net: Herpes Simplex Oralis

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