Optimising CAR T therapy for the treatment of solid tumors

Introduction Adoptive immunotherapy using chimeric antigen receptor (CAR)-engineered T cells has proven transformative in the management of B cell and plasma cel derived malignancies. However, solid tumors have largely proven to be resistant to this therapeutic modality. Challenges include the paucity of safe target antigens, heterogeneity of target expression within the tumor, difficulty in delivery of CAR T cells to the site of disease, poor penetration within solid tumor deposits and inability to circumvent the array of immunosuppressive and biophysical barriers imposed by the solid tumor microenvironment.