Transcript A comprehensive platform for T cell Stimulation based on

Modular biomaterials for immunotherapy
and diagnostics: Carriers for Drug and
Antigen Delivery to Immune Cells
Tarek Fahmy
Yale University
Dept. of Biomedical and Chemical Engineering
Immunoengineering
www.fahmylab.org
APC’s present antigen and create a stimulatory or
inhibitory microenvironment for T cell stimulation
Virus or Bacteria
Tumor Cells
Antigen Processing
DC
B cell
Antigen-presenting cell
(Uptake of Pathogen)
Antigen Display to T
cells in lymph nodes
Peptide/MHC
CD4+
T cell
DC
CD8+
T cell
CD8+
T cell
CD8+
T cell
Activated T Cells
T cells circulate
through body
TCR
CD8+
T cell
Examples of what we Do...
Interface of Materials science and Immunology
1. Pathogen-associated molecular patterns
(PAMPS) on nanocarriers: a paradigm for
engineering new vaccines.
2. Artificial antigen-presenting cells for adoptive
therapy based on IL-2 loaded biodegradable
carriers.
3. Breaking Tumor immuno-inhibition. Nanocarrier
–mediated combinatorial delivery.
4. Directed Delivery for autoimmunity and
transplant rejection
PAMPS on Nanoparticles: An old idea... New Formulation
for vaccines
West Nile
~40-70 nm
DC
Gram-negative
bacteria
HIV
~100 nm
~1000 nm
Pathogen-Recognition Receptors
Example: Toll-Like Receptors (TLRs)
Nanoparticle Vaccine Vector:
PAMP on the outside.
Antigen on the inside.
Antigen
PAMP
Pathogen
Pathogen-Associated Molecular Patterns
(PAMP) Ex: Flagellin, LPS, CpG
Artificial Antigen presenting cells for adoptve
immunotherapy.
Adoptive immunotherapy
IL-2
April 2010: Dendreon Makes History: FDA Approves First Active
Immune-Booster to Fight Cancer. Provenge®
Dendreon Sets Provenge Price at $93,000, Says Only 2,000 People Will
Get it in First Year
The tumor microenvironment is immunoinhibitory. Solution: Combination Delivery
www.fahmylab.org
Postdocs
Fiona Sharp
Ragy Ragheb
Michael Look
Former: Arunima Banerjee
Dongin Kim
Former: Eric Stern
Collaborators
Mark Reed (Nanosensors)
Grad Students
Former: Jason Criscione
Former: Stacey Demento
Former: Tarek Fadel
Former: Michael Look
Former: Erin Steenblock
Former: Jason Park
Enping Hong
Alyssa Siefert
Michael McHugh
Sean Bickerton
Shihan Khan
Su Metcalfe (Parkinsons)
Priti Kumar(HIV)
Michael Caplan (Vaccines)
Mark Saltzman (Biomaterials)
Richard Flavell (Cancer)
Kevan Herold (Diabetes)
Chris Hunter (Parasitic infections)
Daniel Goldstein (Transplantation)
Albert Sinusas (CT/SPECT imaging)
Diane McMahon-Pratt (Leshmaniasis)
Choukri Ben Mamoun (Malaria)
Leiping Chen (Cancer)
Jay Chen (Radiology)