Abstract
Adoptive cell therapy is a notable achievement in the treatment of various hematological malignancies. Among these cell-based therapies, chimeric antigen receptor natural killer (CAR-NK) cells have received increasing attention because, unlike CAR-T cells, they are not associated with the risk of cytokine release syndrome, immune-effector-cell-associated neurotoxicity syndrome, or graft-versus-host disease. CAR-NK cells have enhanced targeting properties and demonstrated therapeutic efficacy against various types of cancer. However, they face substantial challenges, including complex operational procedures, high cost associated with long-term use, and safety concerns. Aptamers are single-stranded oligonucleotides and known as "chemical antibodies" because of their highly specific binding ability to targets. In this study, we designed a multivalent aptamer oligonucleotide complex containing four strands of CD30 aptamers to engineer and functionalize NK cells using click chemistry. Under aptamer guidance, multivalent aptamer oligonucleotide complex NK cells specifically bind to CD30-positive lymphoma cells and trigger more effective antitumor effects than that of parental NK cells, both in vitro and in vivo. Therefore, the proposed approach endows NK cells with tumor-specific targeting ability and enhances their adoptive therapeutic efficiency in CD30-positive lymphoma, showing substantial potential for application in the clinical treatment of malignant lymphoma.