TY - JOUR
T1 - Antibody-platinum (IV) prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma
AU - Yin, Xiangye
AU - Zhuang, Yingjie
AU - Song, Haiqin
AU - Xu, Yujian
AU - Zhang, Fan
AU - Cui, Jianxin
AU - Zhao, Lei
AU - Yu, Yingjie
AU - Zhang, Qixu
AU - Ye, Jun
AU - Chen, Youbai
AU - Han, Yan
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2024/3
Y1 - 2024/3
N2 - Antibody-drug conjugates (ADCs) are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells, thereby attracting considerable attention in precise oncology therapy. Cetuximab (Cet) is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma (cSCC); however, its anti-tumor activity is limited to a single use. Cisplatin (CisPt) shows good curative effects; however, its adverse effects and non-tumor-targeting ability are major drawbacks. In this study, we designed and developed a new ADC based on a new cytotoxic platinum (IV) prodrug (C8Pt(IV)) and Cet. The so-called antibody-platinum (IV) prodrugs conjugates, named Cet-C8Pt(IV), showed excellent tumor targeting in cSCC. Specifically, it accurately delivered C8Pt(IV) into tumor cells to exert the combined anti-tumor effect of Cet and CisPt. Herein, metabolomic analysis showed that Cet-C8Pt(IV) promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells, thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum (IV) prodrugs conjugates.
AB - Antibody-drug conjugates (ADCs) are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells, thereby attracting considerable attention in precise oncology therapy. Cetuximab (Cet) is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma (cSCC); however, its anti-tumor activity is limited to a single use. Cisplatin (CisPt) shows good curative effects; however, its adverse effects and non-tumor-targeting ability are major drawbacks. In this study, we designed and developed a new ADC based on a new cytotoxic platinum (IV) prodrug (C8Pt(IV)) and Cet. The so-called antibody-platinum (IV) prodrugs conjugates, named Cet-C8Pt(IV), showed excellent tumor targeting in cSCC. Specifically, it accurately delivered C8Pt(IV) into tumor cells to exert the combined anti-tumor effect of Cet and CisPt. Herein, metabolomic analysis showed that Cet-C8Pt(IV) promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells, thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum (IV) prodrugs conjugates.
KW - Antibody drug conjugate
KW - Cutaneous squamous cell carcinoma
KW - DNA damage
KW - Platinum drug
KW - Targeted therapy
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U2 - 10.1016/j.jpha.2023.11.002
DO - 10.1016/j.jpha.2023.11.002
M3 - Article
C2 - 38618248
AN - SCOPUS:85184771445
SN - 2095-1779
VL - 14
SP - 389
EP - 400
JO - Journal of Pharmaceutical Analysis
JF - Journal of Pharmaceutical Analysis
IS - 3
ER -