Immunology Division

The Immunology Division seeks to understand the nature of human immune system and tumor antigens including their optimal presentation and the regulatory mechanisms that govern the immune system. The purpose is to develop innovative immunotherapy intervention strategies for the treatment of cancer. 

Immune system and malignant cells often coexist in a dynamic environment. The interaction between growing tumors and the immune system may result the ability of tumors to evade in order to proliferate and metastasize. Antitumor immune response work by two mechanisms i.e. by exerting a direct antitumor effect or by indirectly enhancing the antitumor immune response. Understanding the molecules that regulate tumor growth and evasion such as PD-L1, MHC, interferon regulatory factors and AFP, and the agents that interact with them, is important for the development of antitumor immunotherapy. 

Oncolytic immunotherapy is a cancer treatment that uses the viruses that mediate antitumor activity to induce tumor cells death and generate an immunity against tumors. Newcastle disease virus (NDV) is one of safe and potential oncolytic virus that have been studied in decades for oncolytic agent. NDV oncolytic study has been ongoing at MRIN since 2014 and is now entering pre-clinical trial in mice. 
The Division is equipped with BSL-2 and cell culture facility, ELISA reader, western blotting, flow cytometry and fluorescence microscope that enable us to perform virus and cell culture, analyze the expression of surface markers, extracellular as well as intracellular molecules
Research projects:
1.Potential of NDV as oncolytic and antitumor immunomodulatory agent.
 Our previous study showed  that tumor cell lines originated from lung (A549), brain (U87MG, T98G, TM31,         NP5), breast (MCF7, MDA-MB-453), and liver (Huh7 and HEP-G) were more susceptible to NDV compared to       normal lung fibroblast (HF19), skin fibroblast (NB1RGB), monocytes and transformed kidney cell                           (HEK293T). NDV was found as a potential  interferon (IFN) type I and III in tumor cells, and the                                 accumulation  of NDV-induced IFNs in tumor cells  apparently contributes to oncolysis through apoptosis.       Further study of the strong NDV-induced IFNs showed that NDV in several types of tumor cells                                 downregulated PD-L1 molecules on tumor cells through the upregulation of MHC-class I, which its                       mechanism is still be explored. Those findings provided fundamental of NDV potency for oncolytic agent           and antitumor immunomodulatory agent through the  downregulation of PD-L1 that may boost host                 immune response against tumor.

2. NDV oncolysis in colorectal cancer.
Colorectal cancer (CRC) is a type of cancer that starts in the colon or the rectum and affects men and                  women of all racial and ethnic groups. Our objective of this study is to explore the cytotoxicity of NDV in            CRC cells, its mechanism of death and safety of NDV as oncolytic agent in CRC, as a basis for pre-clinical            study in mouse. Caspases are known as proteins that activated in the early stages of apoptosis, one of                them is Caspase-3, which activated death protease. Our results showed that NDV could induced apoptotic       cell death through activation of Caspase-3 pathway in CRC cells. Moreover, expression of NDV mRNA was           detected in CRC cells by in situ hybridization resembled the presence of NDV replication of NDV without the     production of new virus (tested by TCID50, data not shown). These results lead to support the further study     of NDV oncolysis and antitumor immunomodulatory effect in CRC syngeneic transplanted BALB/c mice.

3.NDV virosome for brain tumor therapy.
Brain cancer has become concern because of their rapid development and the treatments are often fail, so that new treatment strategy is an urge. Virosome is viral vector without genetic material and composed of phospholipid bilayer and surface glycoprotein. Virosome can be constructed from various viruses, including NDV that is known has immunomodulatory effect and safe for human. In our study, NDV virosome was produced by virus lysis and removal of its genetic materials, followed by reconstruction of virus surface proteins. NDV virosome was then confirmed by western blot and transmission electron microscope (TEM), followed by its ability to induce proinflammatory cytokines and oncolytic effect. Produced NDV virosome was confirmed has spherical-shaped with size ranging from 100-500 nm with the main surface glycoproteins and has no genetic material. Brain cancer cell line, NP 5, showed susceptibility to NDV virosome when compared with normal human embryonic kidney cell line, HEK293. This study demonstrated that NDV virosome has potency to be an oncolytic agent, specifically in brain cancer cell line. After all, this study suggested a breakthrough in developing new cancer treatment and will be the basis of NDV virosome application for vaccine, gene therapy, or drug-delivery agent.

4.Expression of SARS-CoV-2 Spike S1 as immunogen for IgY anti-COVID-19 production.
MRIN takes part for acceleration of COVID-19 control in Indonesia through involvement in a research consortium for anti-COVID-19 IgY production, funded by Badan Ristek and Inovasi Nasional. The role of MRIN is to produce large scale immunogen, in the form of SARS-CoV-2 Spike S1 subunit protein, for hyperimmunization in layer chicken. This work is performed by MRIN working group between Immunology, SNP and Molecular Epidemiology divisions.

References by,
Ginting T,Christian S,Larasati Y,Suryatenggara J,Suriapranata I,Mathew G.Scientific reports 2019:9, (1), 1-10
Ginting T,Hidayat N,Christian C,Larasati Y,Nufika R,Yusuf I.Eur. J.Immunol 2019:49, 1684-1685
Ginting T,Suryatenggara J,Christian S,Mathew G.Oncolytic Virother 2017:6, 21-30