Developing a safe and effective CAR T-cell immunotherapy for breast cancer: progress and pitfalls

Current targeted therapies for breast cancer include hormone inhibitors, monoclonal antibodies and tyrosine kinase inhibitors. However, a significant unmet therapeutic need remains for refractory disease and in particular for the triple negative subtype, which lacks hormone receptors and HER2. Chimeric antigen receptors T cells are genetically engineered to deploy selective cytolytic activity against cells that express cognate native target. Durable remissions have been achieved in refractory hematological malignancies but similar success against solid tumors remains elusive. Several hurdles hinder progress, including the need to identify safe antigens, promote T-cell homing to tumor sites and to ensure the persistence of functional chimeric antigen receptors T cells within the immunosuppressive tumor microenvironment. Perspectives to enable the attainment of this goal are presented in this review.