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<p>DS-1471a is a humanized antibody that targets CD147, a transmembrane glycoprotein frequently overexpressed in cancer cells, and has undergone a phase 1 clinical study for advanced solid tumors. To further investigate DS-1471a’s therapeutic potential and the underlying molecular mechanisms involved, we examined its efficacy in patient-derived xenograft (PDX) models of liver cancer. DS-1471a exhibited potent antitumor effects in multiple PDX models, with positive correlations observed between DS-1471a efficacy and expression of CD147 and related proteins such as SMAD4, ARF6, and FBXO22. Among these proteins, overexpression of FBXO22, a ubiquitin ligase, enhanced DS-1471a efficacy in liver cancer xenograft models. Mechanistic analysis showed that FBXO22 overexpression was associated with reduced expression of p21/CDKN1A, a cyclin-dependent kinase inhibitor previously characterized as a degradation target of FBXO22, suggesting a potential regulatory relationship between these proteins. Moreover, in tumor models lacking p21, DS-1471a efficacy was also enhanced, whereas DS-1471a-resistant tumors expressed higher levels of p21 protein. Although direct causal relationships remain to be fully established, these results suggest possible mechanisms underlying DS-1471a efficacy involving not only CD147 expression but also FBXO22 and p21. Taken together, these preclinical findings indicate a potential clinical benefit of DS-1471a and provide useful mechanistic insights for liver cancer treatment.</p>

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Preclinical evaluation and mechanistic analysis of antitumor effects of the novel anti-CD147 antibody DS-1471a in liver cancer models

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月29日

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  • Hiroshi Yuita,
  • Sadanori Watanabe,
  • Jun Tsukada,
  • Yoshikazu Johmura,
  • Sae Aratani,
  • Hirokazu Ishikawa,
  • Ryuichi Nakamura,
  • Miki Yokoyama,
  • Mari Hashimoto,
  • Hideo Yukinaga,
  • Huynh The Hung,
  • Makoto Nakanishi,
  • Keisuke Fukuchi

摘要

DS-1471a is a humanized antibody that targets CD147, a transmembrane glycoprotein frequently overexpressed in cancer cells, and has undergone a phase 1 clinical study for advanced solid tumors. To further investigate DS-1471a’s therapeutic potential and the underlying molecular mechanisms involved, we examined its efficacy in patient-derived xenograft (PDX) models of liver cancer. DS-1471a exhibited potent antitumor effects in multiple PDX models, with positive correlations observed between DS-1471a efficacy and expression of CD147 and related proteins such as SMAD4, ARF6, and FBXO22. Among these proteins, overexpression of FBXO22, a ubiquitin ligase, enhanced DS-1471a efficacy in liver cancer xenograft models. Mechanistic analysis showed that FBXO22 overexpression was associated with reduced expression of p21/CDKN1A, a cyclin-dependent kinase inhibitor previously characterized as a degradation target of FBXO22, suggesting a potential regulatory relationship between these proteins. Moreover, in tumor models lacking p21, DS-1471a efficacy was also enhanced, whereas DS-1471a-resistant tumors expressed higher levels of p21 protein. Although direct causal relationships remain to be fully established, these results suggest possible mechanisms underlying DS-1471a efficacy involving not only CD147 expression but also FBXO22 and p21. Taken together, these preclinical findings indicate a potential clinical benefit of DS-1471a and provide useful mechanistic insights for liver cancer treatment.