Newcastle disease virus (NDV) is an avian virus that causes deadly infection to over 250 species of birds, including domestic and wild-type, thus resulting in substantial losses to the poultry industry worldwide. Many reports have demonstrated the oncolytic effect of NDV towards human tumor cells. The interesting aspect of NDV is its ability to selectively replicate in cancer cells. Some of the studies have undergone human clinical trials, and favorable results were obtained. Therefore, NDV strains can be the potential therapeutic agent in cancer therapy. However, investigation on the therapeutic perspectives of NDV, especially human immunological effects, is still ongoing. This paper provides an overview of the current studies on the cytotoxic and anticancer effect of NDV via direct oncolysis effects or immune stimulation. Safety of NDV strains applied for cancer immunotherapy is also discussed in this paper.

Immunotherapy has raised the attention of many scientists because it hold promise to be an attractive therapeutic strategy to treat a number of disorders. In this study, the immunomodulatory effects of low titers of Newcastle disease virus (NDV) AF2240 on human peripheral blood mononuclear cells (PBMC) were analyzed. We evaluated cytokine secretion and PBMC activation by cell proliferation assay, immunophenotyping and enzyme linked immunosorbent assay. The proliferation of the human PBMC was measured to be 28.5% and 36.5% upon treatment with 8 hemaglutinin unit (HAU) and 2 HAU of NDV respectively. Interestingly, the percentage of cells with activating markers CD16 and CD56 were increased significantly. Furthermore, the intracellular perforin and granzyme levels were also increased upon virus infection. Human PBMC treated with NDV titer 8 HAU was found to stimulate the highest level of cytokine production including interferon-γ, interleukin-2 and interleukin-12. The release of these proteins contributes to the antitumor effect of PBMC against MCF-7 breast cancer cells. Based on the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay, activated human PBMC showed high cytolytic efficiency towards human breast tumor cells. In summary, NDV was able to stimulate PBMC proliferation, cytokine secretion and cytolytic activity.

Problem statement:Immunosuppression is a common approach for pathogens or cancer to escape from immune system of the infected host. Some of the antimicrobe or anticancer drugs may also weaken the body immune system. Among various types of immune cell, natural killer cells are the key component of the innate immunity which plays an important role in first line defense against cancer and microbe infections. Thus, understand the role of Natural killer cell can help to design a successful natural killer cell base therapy in cancer and infectious disease therapy. Approach: Natural killer cell unik activation/inhibition ligand, cytolytic granules and proinflammatory cytokiens offered a specific killing mechanism toward cancer or infected cell target. These specific activation can be achieved in the present of immunomodulator such as cytokines (IL-2 and IL-12) or mitogens (plant extract such as Rhaphidophora korthalsii methanol extract). Results: Key rule of Natural killer cell base immunotherapy is to maintain enough activated Natural killer cell number in the infected host. Conclusion/Recommendations: Future study should expand the clinical use of in vivo or ex-vivo Natural killer cell base therapy especially in cancer treatment.

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