Artificial Cytotoxic T Lymphocytes Selectively Eliminate Tumor Cells for Effective Cancer Therapy.

Abstract

The highly selective ability of cytotoxic T lymphocytes (CTLs) to eliminate tumor cells has inspired the development of artificial nanomedicine for effective cancer therapy. Here, an artificial CTL (aCTL) that selectively recognizes and kills cancer cells is developed. The membrane target-binding moiety, membrane-perforating peptides, and therapeutic prodrugs are integrated into the aCTL through supramolecular interactions. Consequently, the prepared aCTL selectively binds cancer cells and perforates the surrounding membrane. Subsequently, the conjugated prodrug is cleaved and released by the overexpressed membrane transpeptidase, allowing entry into tumor cells through the perforated holes. Finally, the aCTL significantly suppresses the growth of HepG2 hepatocellular carcinoma, B16-F10 melanomas, and patient-derived xenograft (PDX) breast cancer models.