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Prof. Mohamed L. Salem Director, Grants, Innovation & Technology Transfer Center (GITTC)
Director, Center of Excellence in Cancer Research (CECR)
Tanta University
Faculty of Dentistry, Tanta University May 30, 2015
Keys of excellence in research Tanta university as a success story
Microbe Immune
Interaction
Cancer Immune
Interaction
HCV Immune
Interaction
Cancer Biology
CTC/CSC
1894 -1990 1992 – 1995
1995-1997 2010-2014
2001-2010
1 2 1997 - 2001
4 3
5
6
FACULTY OF SCIENCE TANTA UNIVERSITY, EGYPT
Medical Institute of Bioregulation Kyushu University, Japan
Medical University of South Carolina (MUSC) CHARLESTON, SC USA
Cancer Immunotherapy
CD8+ T cells are
specific to the MHC-1
gp10025-33 melanoma
peptide
Donor
Tg
Pmel Culture T cells and stimulate with +
gp10025-33 peptide ± IL12 for 3~5 days
CD44
CD
62
L
Pept + IL12
(pmelIL12 ) Pept alone
(pmelsham )
Our anti-tumor T cell adoptive
transfer model
PBS
CTX
PBS
CTX
Vaccination
+ Poly (I:C)
Phases post CTX treatment relative to adoptive T cell
therapy (Salem, CII 2010)
•Creation of a space niche due to
the induced lymphopenia
•Homeostatic expansion of T cells
•Elimination of regulatory cells
•Elimination of cytokine competition
•Microbial translocation
•Activation of dendritic cells
• Cellular recovery from lymphopenia
• Less of lymphopenia
• Less homeostatic proliferation of T cells
• Expansion of immature dendritic cells
3 6 9 12 15 18
Days after CTX treatment
Nu
mb
er
of
de
nd
riti
c c
ell
s
Lymphopenic phase Recovery phase
0 -1
ACT Antigen priming
+ TLR agonists Antigen boosting
+ TLR agonists
20
DCs
Donor
T cells
CTX
Pmel 12
CTRL
Regression of metastatic melanoma after adoptive
transfer of in vitro activated T cells
Peptide
Mature DCs Monocytes
Monocytes GM-CSF
IL-4
Immature DCs
Tumor
lysate
Viral
vector
MHC class-I
Peptide
complex Inject dendritic cells
Tumor
CTL
Clinical Trial: Pancreatic Cancer Patients
TAG of WAR
Types of Regulatory Cells
Regulatory T cells
Treg cells
MDSC
Immunity
Does cyclophosphamide-containing
chemotherapy increase levels of circulating
MDSCs in breast cancer patients?
ddAC (doxorubicin and cyclophosphamide) every 2 weeks (60/600 mg/m2)
ddT (Paclitaxel every 2 weeks (175 mg/m2))
Pegfilgrastim 6mg SQ
ddAC ddT
R1
R1
Gated on R1
Lin
HLADR
CD
33
CD11b
Normal volunteer
Stage IV breast cancer
ddAC Chemotherapy
1.19%
22.3%
19.6%
R1
Phenotype of MDSC by Whole Blood
Flow Cytometry
Diaz-Montero, et al.
Cancer Immunol Immunother. 2008
MD
SC
(%
)
BL ddAC ddT
12
.55
10
25
MD
SC
/μL
BL ddAC ddT
10
02
50
50
01
00
02
50
0
Increased MDSC levels during ddAC but not
during ddT therapy
n=17
Diaz-Montero, et al.
Cancer Immunol Immunother. 2008
Cell proliferation
IL-2
IFN-
0
2
4
6
8
10
N N P10 P59 P26 P26
BL ddAC
x1
05
ce
lls
22%26%
24%
0.3% 0.55%
3.83%
0
5000
10000
15000
20000
25000
pg
/ml
0
20000
40000
60000
80000
100000
120000
pg
/ml
Decreased T cell responses in cancer patients
correlate with increased levels of MDSCs
Diaz-Montero, et al.
Cancer Immunol Immunother. 2008
Capacity Building
Research Elements
Experience
Expertise
Infrastructure
Skills
Knowledge
Research Needs
Communication
Lab Space
Budget
Manpower
Leadership
Project-based Research
Science
Patents
Publications
Competitiveness Internationalization
Marketing
Levels of Research Capacity Building
Five key elements of an organization’s design
The Star Model
Components of
Research Capacity Development
FACTORS INFLUENCING RESEARCH PRODUCTIVITY (Individual Factors)
• In-depth knowledge of the research area
• Basic research skills
• Socialization
• Advisory/Mentor functioning
• Work habits
• Professional network
• Productive local peer support
• Simultaneous projects
• Sufficient work time and Commitment
• Supportive environment
Personal motivation
FACTORS INFLUENCING RESEARCH PRODUCTIVITY (Institutional Factors)
Phases of Research Capacity Development
Tanta University
Grants, Innovation & Technology Transfer Center (GITTC)
• Technology Transfer Office (TTO)
• Grants and International Cooperation Office (GICO)
• Technology Innovation Support Center (TISC)
Projects per domain submitted to Tanta University Research fund (2011-2013)
Total: 101
Material Sciences 17%
Biotechnology 16%
Water 12%
Integrated Projects
12%
Project No, Hepatitis, 11%
Stem cells 11%
Education & Socialization
8%
Agricultural residues
7%
Renewable Energy 6%
Projects submitted per faculty to Tanta University Research Fund (2011-2013)
0
5
10
15
20
25
30
35
40
45 42
19
16
10
5 3 2 2 1 1 0 0 0
National and International funded projects
(2010-2014)
•> 42 million LE
• Tanta University Central Lab (5m LE; STDF) • Tanta University CECR (10m LE; STDF) • Faculty of Medicine, DTPC (5m LE; STDF) • Faculty of Medicine (2m; 2 projects; STDF) • Faculty of Science (4 projects; 6m; STDF) • Faculty of Agriculture (1 project; Mobility, FP7) • Faculty of Engineering (3 projects, 5m; STDF) • Ministry of Int Cooperation (about 1m) • Academy of Scientific Research & Technology • Ministry of Higher Education (about 10m) Medicine, Engineering, Science, Education
National and International Grants
انجازات الجامعة في الحصول
تنافسيةمشروعات علي
(2010 -2014)
جنيه مليون 40
Center of Excellence in Cancer Research (CECR)
الفريق أثناء توقيع العقد
Overall Aim of The Proposal
1. Establish "Center of Excellence in Cancer Research (CECR)” and furnish the center with three state-of-art equipment, including: – Flow Cytometr
– Next generation microarray platform
– FLEXMAP 3D advanced liquid based multiplexing system which bridging the proteome and the genome.
– Isoflux
2. Perform cutting-edge preclinical and clinical cancer research
Correlate clinical performance with genomic and proteomic profiling of primary tumors with circulating tumor cells (CTCs) and cancer stem cells (CSCs).
Use CTCs and CSCs to genotype for mutated genes as pharmacodynamic data for molecularly targeted drugs.
Wider Objectives of The Proposal
مركز تكنولوجيا البصمة الجينية كأداة لتطوير انشاء األبحاث التطبيقية المتقدمة لتشخيص السرطان
Genetic Signature center for fostering next generation translational
كلية الطب جامعة طنطا
microRNAs: tools for cancer
diagnosis
Affymetrix genechip microarray
Affymetrix genechip microarray
FLEXMAP 3D™ Proteomic System
BD FacsCanto Flow Cytometer
The IsoFlux System delivers
a highly enriched CTC
sample ready for analysis
MiSeq – NGS
52.3 cm
Multidisciplinary team work can build success with
sustainability
To Be • United
• Patient
• Optimistic
• Enthusiastic
• Open minded
• Overcome the obstacles
• Look for new partners
In
Out
Thank you
Thank you