Expressing Surface Expressing Surface Proteins to Target Cancer Proteins to Target Cancer

CellsCells

Joe and BobbyJoe and Bobby

GoalGoal

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

Cancer antigensCancer antigens

Tumor cells express surface Tumor cells express surface molecules mostly specific to cancer molecules mostly specific to cancer = antibody targets= antibody targets

1.1. Detection of tumorsDetection of tumors

2.2. Antibody-dependent cellular Antibody-dependent cellular cytotoxicity (ADCC)cytotoxicity (ADCC)

3.3. Payload deliveryPayload delivery

http://www.antibody.com

Current Antibody-based Cancer Current Antibody-based Cancer TherapyTherapy

Herceptin (trastuzumab)Herceptin (trastuzumab)• Monoclonal antibody that binds to Monoclonal antibody that binds to

HER2/neu receptor in early-stage breast HER2/neu receptor in early-stage breast cancer cellscancer cells

Rituxan (rituximab)Rituxan (rituximab)• Antibody that binds to CD20, a protein Antibody that binds to CD20, a protein

expressed by B cells (normal & expressed by B cells (normal & malignant)malignant)

• Used to combat B cell non-Hodgkin’s Used to combat B cell non-Hodgkin’s lymphoma, B-cell leukemiaslymphoma, B-cell leukemias

Erbitux (cetuximab)Erbitux (cetuximab)• Attaches to external growth factor Attaches to external growth factor

receptor (EGFR), mediates ADCCreceptor (EGFR), mediates ADCC• $30k for 8 weeks$30k for 8 weeks

Purpose of Our AntibodyPurpose of Our Antibody

Cancer-seeking antibody is Cancer-seeking antibody is expressed on surface of bacteria expressed on surface of bacteria carrying a payload (medicine)carrying a payload (medicine)

ProcessProcess

1.1. Discover effective monoclonal Discover effective monoclonal antibodyantibody

2.2. Find gene sequenceFind gene sequence

3.3. Transform gene into bacteriaTransform gene into bacteria

4.4. Bacteria then expresses antibodyBacteria then expresses antibody

1. Discover effective antibody1. Discover effective antibody

Find cancer cells that express Find cancer cells that express exclusive antigensexclusive antigens

StepsSteps1.1. Immunization (mice, rats): generate Immunization (mice, rats): generate

antibody responseantibody response

2.2. Immortalize antibody response as Immortalize antibody response as hybridomashybridomas

3.3. Create monoclonal antibodies from Create monoclonal antibodies from hybridomas; screen antibodieshybridomas; screen antibodies

http://www.antibody.com

2. Find gene sequence2. Find gene sequence

Identify gene that codes for the Identify gene that codes for the antibodyantibody

2.5. Alternatively2.5. Alternatively

Use an antibody that has already been Use an antibody that has already been identified/matched to type of cancer cellidentified/matched to type of cancer cell

3. Transform gene into bacteria3. Transform gene into bacteria

Standard proceduresStandard procedures ListeriaListeria or or E. coliE. coli

4. Bacteria then expresses 4. Bacteria then expresses antibodyantibody

Bacteria (which holds a payload of Bacteria (which holds a payload of medicine/toxins/whatever) expresses medicine/toxins/whatever) expresses cancer-specific antibodycancer-specific antibody

Cancer cells take up bacteriaCancer cells take up bacteria

Interesting?Interesting?

Monoclonal antibody therapy of Monoclonal antibody therapy of cancer cancer http://www.nature.com/nbt/journal/v2http://www.nature.com/nbt/journal/v23/n9/full/nbt1137.html3/n9/full/nbt1137.html

Antibody Solutions Inc (Antibody Solutions Inc (www.antibody.comwww.antibody.com) based in ) based in Mountain ViewMountain View