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

Cancer Med. 2021 Jul;10(14):4677-4696. doi: 10.1002/cam4.4052. Epub 2021 Jun 24.

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.

Keywords: antibody drug conjugate; cancer; targeting ability; therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antigens, Neoplasm / immunology
  • Bystander Effect
  • Clinical Trials as Topic
  • Drug Approval
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy
  • Humans
  • Immunoconjugates / immunology
  • Immunoconjugates / therapeutic use*
  • Molecular Targeted Therapy / methods
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Pancreatic Neoplasms / therapy

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Immunoconjugates