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

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:

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

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

Immune System: “The Simplest Manner:”

Natural Defense MechanismInfective

Pathogens

NeoplasticDisease

Non - Self Abnormal Structures“ANTIGENS”

Immune System:“Immune Scenario”

Antigen

Identification

Immune Response

Disease Effect

Host Effect

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.

Immune System:“Cellular Key-players”

Lymphocytes

T-Cells

CD8+ Identification

CD4+

Th1 Identification

Th2 Identification

Th17Cancer

Autoimmunity

NK CellsLow MHC Class1

+++ KIR

Treg immune

System

B-Cells Plasma Cells Antibodies

Myeloid Cell Macrophages

M1Phagocytosis

& IFN-G

M2 IL4,10 & TGF-B

Pluripotent cell in Bone

Marrow

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 –GIL17

Tumor Cell

CD28 CD80/86

Immune System:“Immune Surveillance & Synapse” = How T-Lymphocyte Can Identify Non-Self Antigen?”

CD28 CD80/86

+++ ---

GITROX40ICOS

CTLA-4PD-1TIM3LAG3

Cytotoxic T Cell

Non Cytotoxic

T Cell

Check Point Molecules

Immune System:“Immunoediting” = “Phases of Tumor Evasion of

Immune Surveillance”

Elimination

EquilibriumEscape

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”

Immune System:Evaluation of Response:

Immune System:Evaluation of Response:

Immune System:Prediction of Response:

• Which Molecule to be tested?

• Which Cut off Point?

Tomorrow?

Continued Efforts – Evaluation of Trials – Cost Benefit

Thank You