Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore (Singapore).
Angew Chem Int Ed Engl. 2014 Jun 23;53(26):6752-6. doi: 10.1002/anie.201402879. Epub 2014 May 20.
There is growing consensus that the clinical therapeutic efficacy of some chemotherapeutic agents depends on their off-target immune-modulating effects. Pt anticancer drugs have previously been identified to be potent immunomodulators of both the innate and the adaptive immune system. Nevertheless, there has been little development in the rational design of Pt-based chemotherapeutic agents to exploit their immune-activating capabilities. The FPR1/2 formyl peptide receptors are highly expressed in immune cells, as well as in many metastatic cancers. Herein, we report a rationally designed multimodal Pt(IV) prodrug containing a FPR1/2-targeting peptide that combines chemotherapy with immunotherapy to achieve therapeutic synergy and demonstrate the feasibility of this approach.
越来越多的人认为，一些化疗药物的临床治疗效果取决于它们的非靶向免疫调节作用。铂类抗癌药物以前被确定为先天和适应性免疫系统的有效免疫调节剂。然而，在合理设计基于铂的化疗药物以利用其免疫激活能力方面进展甚微。FPR1/2 甲酰肽受体在免疫细胞以及许多转移性癌症中高度表达。在此，我们报告了一种合理设计的包含 FPR1/2 靶向肽的多模式 Pt(IV)前药，该前药将化疗与免疫疗法相结合，以实现治疗协同作用，并证明了这种方法的可行性。
