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In this day and age, care of patients involved many disciplines and many health professionals. So it is important for health professionals to come together to learn about diseases and how we manage these diseases together, rather than learn in their own professional silos.








~ Assoc Prof Kevin Tan
Senior Consultant, Neurology, National Neuroscience Institute


Programme >

Immunotherapy Symposium 
Manipulating the Body’s Immune System for Therapeutic Purposes


 Track type: Symposium


 Duration: 90 minutes


 Location: Academia, Level 1, L1-S1


Topic 1:

Treatment of Autoimmune Disease: The Evolution of Immunotherapy in Multiple Sclerosis

Prof David Hafler


Multiple sclerosis is the most common neurologic disease of young adults. It has gone from a non-treatable disease with no clear cause to a highly treatable autoimmune disease where the underlying genetic architecture has been elucidated. The first era began in 1993 with approval of IFN-β to treat relapsing forms of MS followed by the development of glatiramer acetate, a random co-polymer of four amino acids. In placebo controlled and double-blind clinical trials of thousands subjects lasting two years all these agents produced slightly more than 30% reduction in annual relapse rate and magnetic resonance imaging (MRI) disease activity was reduced by a comparable or greater degree. A follow-up study 21 years after the first clinical trial of IFN-β showed a survival benefit for those receiving active drug during the trial as compared with those given placebo.


The second phase of MS therapeutic development came with the approval of natalizumab and of fingolimod in 2009. Natalizumab a mAb to α4 leukocyte arose from preclinical studies using the experimental autoimmune encephalomyelitis model. Given by monthly intravenous infusion, natalizumab exerted impressive inhibitory effects for inflammatory aspects of MS, with >65% reduction in relapses during two years of treatment and >90% suppression of new inflammatory MRI lesions. However, it became clear that in patients who had been exposed to the JC virus, a proportion of patients developed a rare, often-fatal opportunistic brain infection termed progressive multifocal leukoencephalopathy (PML) prompting development of a biomarker, measurement of JC virus ab that proved highly predictive for PML susceptibility. Fingolimod, a pro-drug converted in vivo to a sphingosine 1-phosphate (S1P) analog, down-regulates type 1 S1P receptors on leukocytes and endothelium, trapping naïve and central memory T lymphocytes in lymph nodes and suppressing MS disease activity with 55-60% reduction of relapse rate and reduction of MRI disease activity. Fingolimod lacks target specificity, including those on vascular endothelium, arterial smooth muscle cells, atrial myocytes, bronchial smooth muscle and central nervous system astrocytes and oligodendrocytes.


The third stage of MS therapeutic development involves the oral immunomodulatory medication dimethylfumarate (DMF), which induces the NRF2 transcription factor while blocking NFkB. Alemtuzumab or anti-CD52, a leukocyte depleting monoclonal antibody was recently approved that has comparable immunotherapeutic efficacy to Natalizumab, but is curiously associated with significant induction of other autoimmune diseases. Perhaps most remarkably, Ocrelizumab (CD20) has shown major efficacy in double-blinded, controlled MS treatment trials, with lowering the MRI exacerbation rate to almost zero in one year after infusions 6 months apart. In conclusion, MS has gone from a non-treatable to a highly treatable disease. The major question remains as to whether early treatment of relapsing remitting disease will prevent entry into the more disabling secondary progressive disease.


Topic 2:

Manipulation of Adaptive Autoimmunity

Prof Salvatore Albani

Loss of tolerance to self may lead to systemic autoimmune diseases. We will discuss our specific experience in understanding and manipulation of one such mechanisms in human arthritis.


Topic 3: 

Harnessing the Immune System against Virally-driven Cancers – The Force Awakens

Assoc Prof Toh Han Chong

Cancer immunotherapy has made very significant impact on the lives of patients in many cancers in the last few years. Nasopharyngeal cancer (NPC) is an Epstein Barr virus(EBV)-transformed cancer endemic in South-East Asia and China. I will describe the journey we have taken to demonstrate an alloresponse in the form of a graft-versus-tumour effect to autologous dendritic cell vaccination against EBV latent membrane protein to adoptive T cell therapy with EBV-targeting autologous T cells in the first line treatment of advanced NPC following standard chemotherapy. Translational biomarker analyses will be presented, as will our pre-clinical development of another immune cell type, gamma delta T cells, to target NPC.
Hepatocellular carcinoma (HCC) in this part of the world is associated with Hepatitis B carrier status mainly. Prof Toh will provide an overview of the latest knowledge of the HCC-immune dynamic and clinical advances in using immune-based therapy against HCC. The general principles and roles of current major immunotherapy strategies will be discussed for these two virally-driven prevalent Asian cancers.

*Information is correct at time of update