Barriers and Opportunities for CAR T-Cell Targeting of Solid Tumors

CAR T-cell therapy has transformed the treatment of hematological malignancies of the B cell lineage. However, the quest to fulfil the same promise for solid tumors is still in its infancy. This review summarizes some of the challenges that the field is trying to overcome for effective treatment of human carcinomas, including tumor heterogeneity, the paucity of truly tumor-specific targets, immunosuppression and metabolic restrictions at solid tumor beds, and defective T-cell trafficking. All these barriers are being currently investigated and, in some cases, targeted, by multiple independent groups. With clinical interventions against multiple human malignancies and different platforms under accelerated clinical development, the next few years will see an array of cellular therapies, including CAR T-cells, progressively becoming routine interventions to eliminate currently incurable diseases, as it happened with some hematological malignancies.