1、Antibody-drug Conjugates:Magic Bullets Become RealityWhite PaperJanuary 20252January 2025 Copyright 2025 Citeline,a Norstella company.(Unauthorized photocopying prohibited).Antibody-drug Conjugates:Magic Bullets Become RealityCancer is one of the leading causes of death globally,with a projected 16.

2、3 million deaths by 2040.1 Interventions for the treatment of cancer include surgical resection,radiotherapy,and drug therapy.While effective,the longstanding use of cytotoxic chemotherapy was a precarious balancing act of achieving sufficient antitumor efficacy while minimizing damage to healthy ce

3、lls and debilitating side effects.Consequently,the 1990s saw a move away from traditional chemotherapy towards more targeted approaches,with tumor-specific antigens emerging as unique druggable targets.Targeted biologics such as monoclonal antibodies(mAbs)provided versatile new drug platforms,and in

4、 1997 rituximab became the first mAb approved for cancer in the treatment-resistant B cell lymphoma setting.An explosion in mAb-driven cancer drug development followed,with 141 mAbs currently marketed for the treatment of various forms of cancer(Figure 1).Cancer therapy then was evolving from potent

5、 but somewhat indiscriminate chemotherapy to targeted biological therapy.Proposed by German physician Paul Ehrlich in 1907,the ideal would be a hybrid encompassing the cytotoxicity of chemotherapy with the tumor specificity of a biologic.Early development of chemotherapy had already yielded an array

6、 of cellular toxins too potent to administer systemically,but which could now potentially be linked to an antibody to become a form of“smart chemotherapy,”These antibody-drug conjugates(ADCs)thus had the potential to make Ehrlichs“magic bullet”theory the new tool in the fight against cancer.2Cancer