Introduction to clinical cancer-minded immunotherapy to be familiar with basic concepts, terminology and recently introduced concepts of management.

1. Immunotherapy
“An old dogma & Evolving
insight”
Mohamed Abdulla M.D.
Prof. of Clinical Oncology
Cairo University
SUN Annual Meeting
MSD Symposium
Le Meridien Cairo Airport
Friday 21/10/2016

2. Member of Advisory Board, Consultant, and Speaker for:
• Amgen, Astellas, Astra Zeneca, Hoffman la Roche, Janssen Cilag,
Merck Serono, Novartis, Pfizer, Mundipharma, MSD, Eli Lilly, Bayer.
• The content of this presentation does not relate to any product of a
commercial interest
Speaker Disclosures:

3. Immune System:
“Knowledge; The Story Has No End”

4. Immune System:
“it seems that we have bodyguards”
Thucydides (411 BC):Recovered people can
serve plague patients without catching the
disease.
Louis Pasteur: The principle of VACCINATION.
William Coley: Injection of killed bacteria into
Sarcoma lesions Tumor Shrinkage

5. Immune System:
“The Simplest Manner:”
Natural Defense Mechanism
Infective
Pathogens
Neoplastic
Disease
Non - Self Abnormal Structures
“ANTIGENS”

6. Immune System:
“Immune Scenario”
Antigen
Identification
Immune Response
Disease Effect
Host Effect

7. Immune System:
“Components”
Innate Immune System Adaptive Immune System
Response is non – specific Pathogen & Antigen specific response
Exposure  immediate & maximal
response.
Lag time between exposure and maximal
response
Cell mediated and humoral components Cell mediated and humoral components
No immunological memory Exposure  immunological memory
All forms of life Only in Jawed vertebrates.

8. Immune System:
“Cellular Key-players”
Lymphocytes
T-Cells
CD8+ Identification
CD4+
Th1 Identification
Th2 Identification
Th17
Cancer
Autoimmunity
NK Cells
Low MHC Class1
+++ KIR
Treg
 immune
System
B-Cells Plasma Cells Antibodies
Myeloid Cell Macrophages
M1
Phagocytosis
& IFN-G
M2 IL4,10 & TGF-B
Pluripotent
cell in Bone
Marrow

9. Immune System:
“Immune Surveillance & Synapse” =
How T-Lymphocyte Can Identify Non-Self Antigen?”
CD4/8 T-Lymphocyte
TCR
CD4/8
R
CD3 R
Antigen Presenting Cell
MHC 1
INF –G
IL17
Tumor
Cell
CD28 CD80/86

10. Immune System:
“Immune Surveillance & Synapse” =
How T-Lymphocyte Can Identify Non-Self Antigen?”
CD28 CD80/86
+++ ---
GITR
OX40
ICOS
CTLA-4
PD-1
TIM3
LAG3
Cytotoxic
T Cell
Non
Cytotoxic
T Cell
Check Point
Molecules

11. Immune System:
“Immunoediting” = “Phases of Tumor Evasion of
Immune Surveillance”
Elimination
EquilibriumEscape

12. 1. Loss of Antigenic Machinery  Loss of MHC
Class 1.
2. Infiltration by Treg  -- CD4+ & CD8+
proliferation.
3. +++ Immune Check Point Molecules. (PD-1 &
PD-L1)
Immune System:
“Immunoediting” = “Mechanisms of Tumor
Evasion of Immune Surveillance”

13. Immune System:
Evaluation of Response:

14. Immune System:
Evaluation of Response:

15. Immune System:
Prediction of Response:
• Which Molecule to be tested?
• Which Cut off Point?

16. Tomorrow?
Continued Efforts – Evaluation of Trials – Cost Benefit
Thank You