CARs are sharpening their weapons

The tumor microenvironment hinders CAR T-cell access, activation, and persistence at the tumor site, thereby impacting on the therapeutic efficacy. To tackle these obstacles, ongoing efforts are focusing on further engineering CAR T-cells to enhance their homing, fitness, long-term persistence, and antitumor activity. Advances in genetic modification have prompted the development of armored CAR T-cells equipped with a combination of synergistic elements strengthening their function. These include cytokine release, chemokine receptor expression, immune checkpoint inhibition, gene-editing of inhibitory molecules, or metabolic reprogramming, among others. Multiarmored CAR T-cells may allow addressing the unmet clinical needs of patients with solid tumors or hard-to-treat hematological malignancies who do not benefit from conventional CAR T-cell therapy. Accordingly, several clinical trials are currently assessing the safety and efficacy of these novel CAR constructs.