Cancer Medicine (Jul 2021)

The promising role of antibody drug conjugate in cancer therapy: Combining targeting ability with cytotoxicity effectively

  • Wen‐Qian Li,
  • Han‐Fei Guo,
  • Ling‐Yu Li,
  • Yong‐Fei Zhang,
  • Jiu‐Wei Cui

DOI
https://doi.org/10.1002/cam4.4052
Journal volume & issue
Vol. 10, no. 14
pp. 4677 – 4696

Abstract

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Abstract Introduction Traditional cancer therapy has many disadvantages such as low selectivity and high toxicity of chemotherapy, as well as insufficient efficacy of targeted therapy. To enhance the cytotoxic effect and targeting ability, while reducing the toxicity of antitumor drugs, an antibody drug conjugate (ADC) was developed to deliver small molecular cytotoxic payloads directly to tumor cells by binding to specific antibodies via linkers. Method By reviewing published literature and the current progress of ADCs, we aimed to summarize the basic characteristics, clinical progress, and challenges of ADCs to provide a reference for clinical practice and further research. Results ADC is a conjugate composed of three fundamental components, including monoclonal antibodies, cytotoxic payloads, and stable linkers. The mechanisms of ADC including the classical internalization pathway, antitumor activity of antibodies, bystander effect, and non‐internalizing mechanism. With the development of new drugs and advances in technology, various ADCs have achieved clinical efficacy. To date, nine ADCs have received US Food and Drug Administration (FDA) approval in the field of hematologic tumors and solid tumors, which have become routine clinical treatments. Conclusion ADC has changed traditional treatment patterns for cancer patients, which enable the same treatment for pancreatic cancer patients and promote individualized precision treatment. Further exploration of indications could focus on early‐stage cancer patients and combined therapy settings. Besides, the mechanisms of drug resistance, manufacturing techniques, optimized treatment regimens, and appropriate patient selection remain the major topics.

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