3. Targeting HER2+ breast cancer with antibody based therapeutics

Monoclonal antibodies

Antibodies specific for oncogenic molecules overexpressed in cancer types, used to specifically target cancer cells.

Antibodies targeting different epitopes of molecule

Can have varied functions and be used in combination for improved treatment.

Antibody-drug conjugates (ADCs)

Monoclonal antibodies can be modified to carry chemotherapy agents to bring cytotoxic agents directly to cancer cells and limit the side effects of chemotherapy agents. The drug covalently bind to antibodies and release chemotherapy agents when the antibody binds to the receptor. ADCs are specific to a cell type that overexpresses an antigen target, whereas chemotherapy drugs kill all cells that proliferate fast. ADCs has longer half-life and require fewer infusions than regular chemotherapy drugs. They can also activate the immune system by binding to Fc receptors on immune cells.

HER2 over-expression

In breast cancer, excessive HER2 receptors leading to rapid cell growth.

Limitations of traditional chemotherapy compared with ADCs

Lack of tumor specificity, dose-limiting toxicity, narrow therapeutic index, and difficulty in dose adjustment.

Advantages of ADCs compared with traditional chemotherapy

Efficient and specific drug delivery, lower doses, increased specificity, and larger therapeutic window.

Desired attributes of antigen for newer ADC components

High homogenous tumor expression, low or no healthy tissue expression, high affinity for antibody recognition

Desired attributes of antibody for newer ADC components

High affinity for antigen recognition, decrease immunogenicity for chimeric or humanized antibodies, longer half-life, and high molecular weight.