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.
