CAR-T cells have shown remarkable initial efficacy for the treatment of otherwise intractable cancers, particularly B-cell malignancies. However, CAR-T therapies are applicable to only a subset of cancers and are limited by low signaling efficiency: a few hundred or more antigen molecules are required to activate a CAR T cell whereas a single peptide-loaded MHC molecule is sufficient to trigger the activation of a normal T cell. This low antigen sensitivity not only limits the current CAR-T therapy to high antigen-expressing cancers, but also results in high frequencies of relapse, during which high antigen-expressing cancers downregulate their antigen levels to escape CAR-T’s attacking. To address these key challenges in the field, we have engineered CARs by including intrinsically disordered regions (IDRs) that promote signaling condensation. The new “IDR CARs” displayed enhanced cytokine production and cytotoxicity towards low antigen-expressing cancer cells in vitro and improved anti-tumor efficacies in vivo. The development of IDR CARs provides a new strategy to reduce the relapse frequency during CAR-T therapy and is expected to broaden CAR T application to low antigen-expressing cancers.