http://www.fao.org/asiapacific/events/detail-events/en/c/1440/

1. Newcastle Disease Virus :
from poultry vaccine to malignancy hero
Khatijah Yusoff, PhD
Faculty of Biotechnology and Biomolecular Sciences
Universiti Putra Malaysia
“FAO Regional Meeting on Agricultural Biotechnologies in Sustainable Food Systems
and Nutrition in Asia-Pacific”

2. “Begin with the end in mind”
Stephen Covey

4. Food Security exists when all people, at
All times, have physical and economic
access to sufficient, safe and nutritious
food to meet their dietary needs and
food preferences for an active and
healthy lifestyle.
- World Food Summit 1996

5. Factors
contributing or
aggravating food
security
Increase in world
population
Poverty
Agricultural land decreasing
Increase food prices
Natural
calamities
Rise of oil price
Climate change
Biofuel production
World trade rules
Wars & conflicts

7. Source by : Consultative Group for International Agricultural Research (CGIAR)
60%

9. ‘Malaysia was ranked at the 35th spot out
of 113 countries in the Global Food Security
Index 2016 rankings’

10. The National Agro-food
policy 2011 – 2020
- Launched by the Malaysia Prime Minister
on 14 January 2012.
Focuses on improving the efficiency
of agro-food industries along the
value chain, so that the industry will
be more productive and competitive
by emphasising on the aspect of
knowledge.

11.  8 main ideas have been identified to support the transformation
process of the agro-food industries which are:
1) Food sources guarantee – availability, safety and affordability;
2) Development of high value agriculture
3) Planning and development of sustainable agriculture;
4) Dynamic agricultural clusters, maximizing income generations among
agro entrepreneurs;
5) Private investors are catalyst for modern agricultural transformation;
6) Knowledgeable and informed agriculture human capital;
7) Agricultural modernization centered on research (R&D) and
innovations; and
8) Excellence of agricultural support services

12. Sources of Proteins for Human
Consumption
Fish Lamb Beef Pork Poultry
Affordable ✔ ✗ ✗ ✔ ✔
Available all
year round
✗ ✔ ✔ ✔ ✔
Global
Acceptance
✔ ✗ ✗ ✗ ✔

14. Malaysians consume
~ 28 kg poultry meat, ~200 eggs

15.  RM 5 billion per annum
 3755 farms  480 million birds per annum
 Frequent outbreaks of infectious diseases
• Infectious bronchitis virus
• Chicken anemia virus
• Infectious bursal disease virus
• Avian pox virus
• Avian influenza virus
• Newcastle disease virus
 Shortage in poultry meat
Poultry Industry in Malaysia

16.  Avian paramyxovirus serotype-1
(APMV-1)
 Firstly isolated in 1926 in
Newcastle-upon-Tyne, England and
the Island of Java, Indonesia
 Pathotypes:
• Lentogenic
• Mesogenic
• Velogenic
Newcastle Disease Virus (NDV)
http://www.lionsgrip.com/chickensnewcastle.html

17. NDV Infects > 206 Species of Birds

18.  Frequent outbreaks of Newcastle
disease
 ~ 100% mortality
 Trade barriers
 Severe economic loss
 > RM 100 million for Malaysia
 Causes
 Spread through infected birds’
droppings and secretions; rapidly in
confined birds
 Vaccination failure
 Immunosuppressive agents
 Difficulty in early detection of NDV
Newcastle Disease Virus

19. GENOME ANALYSIS
CLONING & EXPRESSION
STRUCTURAL
ANALYSIS
P L
NP: RNA
PROTEIN-PROTEIN
INTERACTIONS
VIRUS TRANSMISSION PATHOGENESIS BIOLOGICS
PATENTS
NANOBIOTECHNOLOGY
VIROTHERAPY
VACCINES
NP M F HN LP
3’ 5’
~15 kb
NDV

20. TLTTKLY, SWGEYDM – linear peptides CTLTTKLYC – cyclic peptide
PI 20013687; Ramanujam et al., 2002; 2004; Ji et
al., 2005; Lee et al., 2006
Peptides: Inhibition of NDV Propagation

21. NDV Vaccine

22. NDV as an Oncolytic Virus
• First report in the early 1950s
• Advantages:
– Tumour selective replication and safety profile
Selectively bind and infect the tumour cells
Replicate 10,000 time faster in tumour cells than in normal cells
Virus is not pathogenic to humans
– Oncolytic potential
Direct killing via replication
Induce apoptosis
– Immunostimulatory properties
Enhanced expression of viral antigen on tumour cell surfaces
Induces synthesis of cytokines – IFN and TNF

23. How does NDV kill the cancer?
Oncolysis
Direct Indirect
Intrinsic Pathway
• Membrane
permeabilization
• Caspase-9 activation
• Pro-apototic HN, M, L &
F proteins
Extrinsic Pathway
Receptor tyrosinase
kinase,RTK Pathway
ER Stress Pathway
Adaptive Immunogenecity
Innate Immunogenecity
NDV infected cells expresses HN & F
protein on the cell surface
•Attracts erythrocytes & lymphocytes
•Generates Tumor infiltrating
lymphocytes (TIL)
Activates macrophages,
monocytes and NK cells

24. Clinical Trials of Oncolytic Viruses:
Tumour Regression
Jennerex Biotherapeutics
Vaccinia virus JX-594 (Pexa-Vec)
Advanced hepatocellular carcinoma
(HCC) Complete response. Heo et al.,
2013. Nature Medicine 19, 329-336.

25. Clinical Trials of Oncolytic Viruses:
Improved Survival
Oncolytics Biotech, Reolysin® , Metastatic melanoma Improved survival
Galanis et al., 2012. Mol Ther 20, 1998-2003.

26. FDA Approval: Landmark for
Oncovirotherapy

27. Current Research Direction
• Develop recombinant NDV AF2240 armed with immunomodulatory
gene(s)
Improve killing of cancer and saving normal cells
• NGS profile of genome-transcriptome of sensitive, resistant and persistently
infected cancer cells
Identify predictive biomarkers of response and
functional modulators that can supplant persistency of infection
rNDV in clinical trials for selective subset of cancers

28. Balancing Profitability & Humanity
Mortality
Benefits

29. Acknowledgements
My research team

30. TERIMA KASIH / THANK YOU
kyusoff@upm.edu.my