CTLA4 and cancer: The first report using aptamers to manipulate immune responses against cancer by antagonizing the immune checkpoint receptor CTLA-4 was the development of RNA aptamers that could bind CTLA-4 with high affinity and specificity and inhibited CTLA-4 function in vitro and enhanced tumor immunity in mice; tetrameric assemblies of the aptamers could improve their bioactivity significantly both in vitro and in vivo [149].