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Therapeutic Cancer Vaccines
Edgar G. Engleman, MD
The Immune System
• The immune system is our major defense
against viruses, tumors and other “foreign
invaders”
• It uses white blood cells and antibodies to fight
invaders
• The immune system is extraordinarily precise
and powerful, and when successfully deployed,
its targets are destroyed with little or no
collateral damage
Tumors and the Immune System
• Tumors present a unique challenge because
they consist mainly of normal tissue components
(“self”) and the immune system is trained to
avoid attacking self
• The solution is to either overcome the reluctance
of the patient’s immune system to attack the
tumor, or produce tumor-specific antibodies or
white blood cells outside of the body and inject
them into patients
Immunotherapy with Monoclonal
Antibodies
• Antibodies recognizing constituents of tumors
can be produced using recombinant DNA
methods
• These antibodies, when injected into patients,
are safe and well tolerated and are becoming
standard treatments for several types of tumors
• But each antibody recognizes only a single
tumor constituent, must be administered
repeatedly over time, and is only partly effective
Redirecting the Immune System
Against Cancer Using Vaccines
• Old concept: the inability of the immune
system to recognize and attack tumors is
inherent and irreversible
• New discovery: the old concept is false.
By introducing tumor constituents directly
to the sentinels of the immune system
(dendritic cells), potent anti-tumor
immunity is generated
Dendritic Cells (DC) are Present in Blood
and Most Tissues
Blood DC
A
Skin
Langerhans cells
B
Kidney DC
C
Rat Tracheal DC
Murine Tracheal DC
E
Heart DC
F
D
Human Bronchiole DC
G
Dendritic Cells: Center of the “Immuniverse”
Lymph node
Bone Marrow
Stem cell
CD34+
CD8
5
1
DC progenitor production
in the bone marrow
Induction of an
immune response
CD4
DC
NK
B
Antibodies
2 Migration to
peripheral tissue
4 Migration to
lymph nodes
Epidermis
Langerhans cells
Dermis
Lymphatics
Dermal DC
3 Sampling of the environnment
Skin
“danger signals”
e.g. foreign matter
Dendritic Cells (DC) as Therapeutic Vaccines
• Goal: Induce anti-tumor immunity using DC
pulsed with tumor components
• Methods
– Obtain DC from patient blood
– Load DC with tumor components
– Return DC to patients
Preparation and Administration of DC Vaccine
Tumor
Ag
Leukapheresis
DC Generation and
Maturation
Ag loading
Immune & Clinical Monitoring
Vaccination
Ag-Loaded DC
Successful Therapeutic Vaccination
in a Patient with Metastatic Colon Cancer
Dendritic Cell Vaccination for the
Treatment of Prostate Cancer
From: Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee
SS, Jones LA, and Hershberg RM. Placebo-controlled phase III trial of immunologic therapy with
Sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate
cancer. J Clin Oncol 24:3089-94, 2006
The Future for Immunotherapy is
Bright
• More monoclonal antibodies, including
antibodies to prostate cancer
• Drugs that target and activate dendritic cells
• Drugs that target and activate other white
blood cells – T cells, NK cells, B cells