Expressing Surface Proteins to Target Cancer Cells Joe and Bobby.

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Presentation transcript:

Expressing Surface Proteins to Target Cancer Cells Joe and Bobby

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

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

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

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

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)

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

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

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

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

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

Interesting? Monoclonal antibody therapy of cancer v23/n9/full/nbt1137.html Monoclonal antibody therapy of cancer v23/n9/full/nbt1137.html v23/n9/full/nbt1137.html v23/n9/full/nbt1137.html Antibody Solutions Inc ( based in Mountain View Antibody Solutions Inc ( based in Mountain Viewwww.antibody.com