NDV as an Oncolytic Agent – Study in Cancer Cell Lines

Introduction

Virotherapy with oncolytic viruses (OVs) has become the pivotal point of expeditiously growing cancer research. Conclusive data has been found that oncolytic virotherapy, by itself or in combination with chemotherapy, surgery or radiotherapy, considerably impacts deaths due to cancer and increases the remission rate ^{1, 2}.

Oncolytic virotherapy involves the use of OVs which are natural or can also be genetically transformed viruses that are capable to selectively infect and kill cancer cells and effectively spare the healthy cells. This specificity depends on two key mechanisms for productive viral infection and causes host cell lysis. The first one being receptor-mediated uptake, where cancer cells overexpress virus entry specific receptors and second one involves virus adaptation to the host cancer signaling pathways for viral replication ^{3, 4}. Some examples of OVs are Adenovirus, Reovirus, Herpes Simplex virus and NDV ⁵. Newcastle disease virus is one of the most economically important avian viruses which causes infection in domestic poultry, other bird species and thus affects the poultry industry worldwide ⁶. It is commonly known as the Ranikhet disease virus in India. It is ssRNA virus belonging to the Avulavirus genus of the paramyxoviridae family and is called Avian Paramyxovirus type 1(APMV-1) ⁷. While NDV is pathogenic to birds, in humans it is known to be avirulent and causes symptoms identical to flu or laryngitis and conjunctivitis ⁸. It is classified into three pathogenic types based on the disease severity that it causes in birds: (i) Velogenic (virulent), (ii) mesogenic (intermediate), and (iii) lentogenic (avirulent) ². Cassel and Garret were the first scientist to report the anti-cancer effect of NDV in 1965 ⁹. NDV induces an oncolytic effect by several mechanisms which have been confirmed in various cancer cell lines. First and foremost is by directly causing infection and then replicating in cancer cells. Normal cells quickly undergo apoptosis on virus infection, resulting in abortive infection, while cancer cells which have acquired apoptosis resistance survive longer, leading to production of more virus particles and initiating new replication cycles ^{10, 11}. The non-lytic strains, present the viral proteins on the tumor cell membrane post infection and thus are capable to initiate and enhance the immune response ^{3, 12}.