Upon target recognition and binding of the antibody on the tumor cell surface, rapid internalization of the ADC is important for effective payload delivery. This functionality prevents cross-reactivity to other antigens, preventing the ADC from being distributed to other tissues and target cells before reaching the intended site of action and causing off-target toxicity. Highly selective antibodies for a tumor-associated antigen and minimal immunogenicity are the essential characteristics of ADC antibodies. Optimal ADC antigens are highly expressed on the tumor cell surface with restricted or no expression on normal (healthy) cells. Selection of the best target tumor antigen on the cell surface can be a key determinant of ADC activity. The antibody component of the ADC acts as a precision nanocarrier for the chemotherapeutic payload. Pharmaceutical companies are embracing the concept of ADCs, with 12 ADCs approved by the FDA, 2 and advances in the development of targeted delivery vehicles over standard antibodies are improving the performance of these drugs and expanding their potential for the treatment of new cancers. As a result, ADCs offer a wider therapeutic window compared to traditional systemic chemotherapy. The targeting specificity and local release of cytotoxic chemotherapeutics within the tumor micro-environment provide increased anti-tumor efficacy and a decreased systemic toxicity. These tripartite structures, consisting of a targeting antibody and drug payload connected via a linker, render the drug inert as it circulates the body until it is released and activated in the target cell. Increasing adverse side effects from small molecule chemotherapeutics can prevent patient compliance, requiring new precision medicine solutions to bring hope to this field.Īntibody-drug conjugates (ADCs) allow potent chemotherapeutics to be targeted to their intended site of action. By Hyun Yong Cho and Byeong Sung Lee, Pinotbio, Inc.Ĭhemotherapy has always been a delicate balance between maximizing tumor cell death and minimizing off-target toxicity.
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