Prime-Boost Immunization Eliminates Metastatic Colorectal Cancer by Producing High-Avidity Effector CD8⁺ T Cells.

ABSTRACT: Heterologous prime-boost immunization with plasmid DNA and viral vector vaccines is an emerging approach to elicit CD8⁺ T cell-mediated immunity targeting pathogens and tumor Ags that is superior to either monotherapy. Yet, the mechanisms underlying the synergy of prime-boost strategies remain incompletely defined. In this study, we examine a DNA and adenovirus (Ad5) combination regimen targeting guanylyl cyclase C (GUCY2C), a receptor expressed by intestinal mucosa and universally expressed by metastatic colorectal cancer. DNA immunization efficacy was optimized by i.m. delivery via electroporation, yet it remained modest compared with Ad5. Sequential immunization with DNA and Ad5 produced superior antitumor efficacy associated with increased TCR avidity, whereas targeted disru

SUBMITTER: Xiang B 

PROVIDER: S-EPMC5435941 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature