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<p>Antibody-drug conjugates (ADCs), a revolutionary tumor therapeutic modality integrating the targeting specificity of monoclonal antibodies and the cytotoxicity of payloads, have undergone four generations of development, with over 20 approved drugs and more than 300 candidates in clinical trials globally. Despite their remarkable success in treating both hematological malignancies and solid tumors, traditional ADCs still face intractable challenges, including heterogeneity in target antigen expression, insufficient internalization, payload-mediated drug resistance, and severe treatment-related adverse events. This review elaborates on the latest design optimization strategies and research advances of next-generation function-enhanced ADCs, focusing on four core directions: bispecific ADC construction, internalization efficiency improvement, binding affinity enhancement, and payload combination innovation.</p>

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Recent advances in function-enhanced antibody-drug conjugates: Antibody optimization and payload combination

  • 期刊论文

  • 发表日期：

    2026年7月17日

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  • Xin-tong Liu,
  • Feng Tang,
  • Wei Huang

摘要

Antibody-drug conjugates (ADCs), a revolutionary tumor therapeutic modality integrating the targeting specificity of monoclonal antibodies and the cytotoxicity of payloads, have undergone four generations of development, with over 20 approved drugs and more than 300 candidates in clinical trials globally. Despite their remarkable success in treating both hematological malignancies and solid tumors, traditional ADCs still face intractable challenges, including heterogeneity in target antigen expression, insufficient internalization, payload-mediated drug resistance, and severe treatment-related adverse events. This review elaborates on the latest design optimization strategies and research advances of next-generation function-enhanced ADCs, focusing on four core directions: bispecific ADC construction, internalization efficiency improvement, binding affinity enhancement, and payload combination innovation.