Gene-modified dendritic cell vaccines for cancer.

Abstract

Dendritic cell (DC) vaccines are an immunotherapeutic approach to cancer treatment that use the antigen-presentation machinery of DCs to activate an endogenous anti-tumor response. In this treatment strategy, DCs are cultured ex vivo, exposed to tumor antigens and administered to the patient. The ex vivo culturing provides a unique and powerful opportunity to modify and enhance the DCs. As such, a variety of genetic engineering approaches have been employed to optimize DC vaccines, including the introduction of messenger RNA and small interfering RNA, viral gene transduction, and even fusion with whole tumor cells. In general, these modifications aim to improve targeting, enhance immunogenicity, and reduce susceptibility to the immunosuppressive tumor microenvironment. It has been demonstrated that several of these modifications can be employed in tandem, allowing for fine-tuning and optimization of the DC vaccine across multiple metrics. Thus, the application of genetic engineering techniques to the dendritic cell vaccine platform has the potential to greatly enhance its efficacy in the clinic.