SignificanceCircular RNAs (circRNAs) are a unique class of RNAs that are highly stable compared to linear mRNAs and can be engineered to provide durable protein expression. This study demonstrates that circRNA encoding antigenic protein sequences delivered by a charge-altering releasable transporter can effectively serve as both an adjuvant and an immunogen, inducing potent cellular immunity and leading to tumor clearance when used as a therapeutic vaccine. These results suggest engineered circRNAs for the development of vaccines and therapeutics.