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.