1. Novel Technique for Early Detection of Pancreatic Cancer
7/28/10
Payam Chini, MD
Rony Francois, MD/Ph.D. Candidate
Francisco Delgado, Ph.D. Candidate
Tal Salz, Ph.D. Candidate
Process by which large quantities of antibodies (targeted against a particular antigen X) can be produced.
A mouse is immunized by injection of an antigen X to stimulate the production of antibodies targeted against X. The antibody forming cells are isolated from the mouse's spleen.
Monoclonal antibodies are produced by fusing single antibody-forming cells to tumor cells grown in culture. The resulting cell is called a hybridoma.
Each hybridoma produces relatively large quantities of identical antibody molecules. By allowing the hybridoma to multiply in culture, it is possible to produce a population of cells, each of which produces identical antibody molecules. These antibodies are called "monoclonal antibodies" because they are produced by the identical offspring of a single, cloned antibody producing cell.
Once a monoclonal antibody is made, it can be used as a specific probe to track down and purify the specific protein that induced its formation.

2. Pancreatic Cancer Mortality
U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2006 Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; Available at:

3. Why pancreatic cancer has such a high mortality?
Advanced stage of disease once diagnosed
Most patients experience symptoms late in the course of disease

4. How do we diagnose pancreatic cancer?CT
High sensitivity for tumors greater than 2.0cm
Significant decline in sensitivity for smaller lesions
Endoscopic Ultrasound
More sensitive than CT for detecting smaller lesions
Very operator dependent
Difficult to identify lesions in setting of chronic pancreatitis
MRI
Less sensitive than CT and EUS for detecting Pancreatic Cancer

5. Screening for Pancreatic Cancer
An ideal imaging protocol would identify pancreatic cancer early
Allow implentation of a screening program for high risk population

6. Innovation Improve detection of Pancreatic Cancer
Utilize tropism of oncolytic virus
Nanotechnology
Improve detection of Pancreatic Cancer

7. Normal Pancreatic Ductal Cells Pancreatic Cancer Cells
Oncolytic Viruses
Oncolytic Virus
Newcastle Disease Virus (NDV)
Selectively infects human cancer cells
Anti-tumor activity in humans
Normal Pancreatic Ductal Cells
Pancreatic Cancer Cells

8. Nanoparticles
Man-made structures on the scale of 1-100nm
Unique properties not seen with materials on larger scales
Favorable profile of interaction with cell surface

9. Formulated from highly cross-linkable polymers in variety of forms
Nanoparticles
Formulated from highly cross-linkable polymers in variety of forms
Surface functionalization can create “targetable” nanoparticles
Can be loaded with contrasts agents such as Gadolinium and Ferric ammonium citrate

10. Specific Aim 1
Develop MRI-detectable nanoparticles conjugated to antibodies against pancreatic tumor cell antigen for the purpose of early detection of pancreatic cancer
MRI-detectable nanoparticles
Antibody against malignant pancreatic cells

11. tumor cells that are associated with Newcastle Disease Virus
Specific Aim 1.1- Identify and purify the surface antigens of pancreatic
tumor cells that are associated with Newcastle Disease Virus
Tumor antigen
Mass spectrometry
Immunoprecipitation

12. Immunization with Antigen
Specific Aim 1.2: Generate pancreatic tumor specific antibodies
and conjugate them to MRI-detectable nanoparticles
Immunization with Antigen
Myeloma cells
plasma cells
Monoclonal Ab
Nano particle
Process by which large quantities of antibodies (targeted against a particular antigen X) can be produced.
A mouse is immunized by injection of an antigen X to stimulate the production of antibodies targeted against X. The antibody forming cells are isolated from the mouse's spleen.
Monoclonal antibodies are produced by fusing single antibody-forming cells to tumor cells grown in culture. The resulting cell is called a hybridoma.
Each hybridoma produces relatively large quantities of identical antibody molecules. By allowing the hybridoma to multiply in culture, it is possible to produce a population of cells, each of which produces identical antibody molecules. These antibodies are called "monoclonal antibodies" because they are produced by the identical offspring of a single, cloned antibody producing cell.
Once a monoclonal antibody is made, it can be used as a specific probe to track down and purify the specific protein that induced its formation.

13. Specific Aim 1.3: Test antibody-conjugated nanoparticles
in vivo using pancreas cancer mouse model
inject
MRI
Process by which large quantities of antibodies (targeted against a particular antigen X) can be produced.
A mouse is immunized by injection of an antigen X to stimulate the production of antibodies targeted against X. The antibody forming cells are isolated from the mouse's spleen.
Monoclonal antibodies are produced by fusing single antibody-forming cells to tumor cells grown in culture. The resulting cell is called a hybridoma.
Each hybridoma produces relatively large quantities of identical antibody molecules. By allowing the hybridoma to multiply in culture, it is possible to produce a population of cells, each of which produces identical antibody molecules. These antibodies are called "monoclonal antibodies" because they are produced by the identical offspring of a single, cloned antibody producing cell.
Once a monoclonal antibody is made, it can be used as a specific probe to track down and purify the specific protein that induced its formation.

14. Conclusion and Future Studies
Modalities for early detection of pancreatic cancer needed
Our proposal
Novel technique utilizing the properties of oncolytic viruses and nanoparticles
Will lay the foundation for future studies that will test this technology in human subjects

15. Group Leaders: Acknowledgements Dr. Philipp Dahm, MD
Dr. Keith Muller, Ph.D.

16. Questions?
Process by which large quantities of antibodies (targeted against a particular antigen X) can be produced.
A mouse is immunized by injection of an antigen X to stimulate the production of antibodies targeted against X. The antibody forming cells are isolated from the mouse's spleen.
Monoclonal antibodies are produced by fusing single antibody-forming cells to tumor cells grown in culture. The resulting cell is called a hybridoma.
Each hybridoma produces relatively large quantities of identical antibody molecules. By allowing the hybridoma to multiply in culture, it is possible to produce a population of cells, each of which produces identical antibody molecules. These antibodies are called "monoclonal antibodies" because they are produced by the identical offspring of a single, cloned antibody producing cell.
Once a monoclonal antibody is made, it can be used as a specific probe to track down and purify the specific protein that induced its formation.