AI Article Synopsis
- CAR T cell therapy faces significant challenges when targeting solid tumors, particularly due to obstacles like the tumor vasculature's anergic state and low levels of adhesion molecules.
- The solid tumor microenvironment also includes immunosuppressive factors that hinder CAR T cell infiltration and effectiveness.
- Redirecting CAR T cells towards tumor vasculature and engineering them for better trafficking and safety are potential strategies to enhance the therapy's efficacy against solid tumors.
Article Abstract
For successful application of chimeric antigen receptor (CAR) T cell therapy in solid tumors, major hurdles have to be overcome. CAR T cells have to cross the vascular barrier, which is hampered by the anergic state of the tumor vasculature, characterized by suppressed levels of leukocyte adhesion molecules on the endothelium. Additional immunosuppressive mechanisms in the solid tumor microenvironment can affect infiltration, activity and persistence of CAR T cells. Redirecting CAR T cells towards the tumor vasculature poses a possible solution, as molecular targets of tumor endothelial cells can be directly engaged from within the blood. In this review, we discuss recent advances in CAR T cell therapy against solid tumors, with a focus on targeting the tumor vasculature. Furthermore, we discuss opportunities to overcome challenges and barriers through engineering of CAR T cells to enhance trafficking, safety and efficacy.
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| http://dx.doi.org/10.1016/j.bbcan.2022.188701 | DOI Listing |
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