Embodiments of the disclosure encompass methods and compositions related to targeting of tumor antigen-positive cells with therapy using cells that express a chimeric antigen receptor that targets the tumor antigen-positive cells in the presence of None or more interleukins that enhance efficacy of the tumor antigen-specific chimeric antigen receptors. In specific embodiments, the tumor antigen is glypican-3 and the one or more interleukins are EL-15 and EL-21.