1. Expressing Surface Proteins to Target Cancer Cells Joe and Bobby

2. Goal To localize medicine-carrying bacteria to cancer cells To localize medicine-carrying bacteria to cancer cells

3. Cancer antigens Tumor cells express surface molecules mostly specific to cancer = antibody targets Tumor cells express surface molecules mostly specific to cancer = antibody targets 1.Detection of tumors 2.Antibody-dependent cellular cytotoxicity (ADCC) 3.Payload delivery http://www.antibody.com

4. Current Antibody-based Cancer Therapy Herceptin (trastuzumab) Herceptin (trastuzumab) Monoclonal antibody that binds to HER2/neu receptor in early-stage breast cancer cellsMonoclonal antibody that binds to HER2/neu receptor in early-stage breast cancer cells Rituxan (rituximab) Rituxan (rituximab) Antibody that binds to CD20, a protein expressed by B cells (normal & malignant)Antibody that binds to CD20, a protein expressed by B cells (normal & malignant) Used to combat B cell non-Hodgkin’s lymphoma, B-cell leukemiasUsed to combat B cell non-Hodgkin’s lymphoma, B-cell leukemias

5. Erbitux (cetuximab) Erbitux (cetuximab) Attaches to external growth factor receptor (EGFR), mediates ADCCAttaches to external growth factor receptor (EGFR), mediates ADCC $30k for 8 weeks$30k for 8 weeks

6. Purpose of Our Antibody Cancer-seeking antibody is expressed on surface of bacteria carrying a payload (medicine) Cancer-seeking antibody is expressed on surface of bacteria carrying a payload (medicine)

7. Process 1. Discover effective monoclonal antibody 2. Find gene sequence 3. Transform gene into bacteria 4. Bacteria then expresses antibody

8. 1. Discover effective antibody Find cancer cells that express exclusive antigens Find cancer cells that express exclusive antigens Steps Steps 1.Immunization (mice, rats): generate antibody response 2.Immortalize antibody response as hybridomas 3.Create monoclonal antibodies from hybridomas; screen antibodies http://www.antibody.com

9. 2. Find gene sequence Identify gene that codes for the antibody Identify gene that codes for the antibody 2.5. Alternatively Use an antibody that has already been identified/matched to type of cancer cell Use an antibody that has already been identified/matched to type of cancer cell

10. 3. Transform gene into bacteria Standard procedures Standard procedures Listeria or E. coli Listeria or E. coli

11. 4. Bacteria then expresses antibody Bacteria (which holds a payload of medicine/toxins/whatever) expresses cancer-specific antibody Bacteria (which holds a payload of medicine/toxins/whatever) expresses cancer-specific antibody Cancer cells take up bacteria Cancer cells take up bacteria

12. Interesting? Monoclonal antibody therapy of cancer http://www.nature.com/nbt/journal/ v23/n9/full/nbt1137.html Monoclonal antibody therapy of cancer http://www.nature.com/nbt/journal/ v23/n9/full/nbt1137.html http://www.nature.com/nbt/journal/ v23/n9/full/nbt1137.html http://www.nature.com/nbt/journal/ v23/n9/full/nbt1137.html Antibody Solutions Inc (www.antibody.com) based in Mountain View Antibody Solutions Inc (www.antibody.com) based in Mountain Viewwww.antibody.com