November 12, 2020
Although chimeric antigen receptor T‐cell (CAR‐T) therapy has not garnered the same success with solid tumors, including brain tumors, that it has had with hematological malignancies, current strategies to improve effector function of CAR-T therapy provide hope, researchers wrote in a review paper published in Molecular Therapy.
“In the last decade, investigators have developed elegant solutions and/or countermeasures in preclinical studies, engineering CAR T-cells with significantly improved effector function and/or combining them with other treatment modalities,” explained researchers from St. Jude Children’s Research Hospital. “Thus, we strongly believe that the future of CAR T-cells for solid tumors is bright, and they will not become a mere footnote in the history of cancer immunotherapy.”
The authors described a handful of roadblocks prohibiting success of CAR T-therapy for solid tumors in early-phase clinical studies, including the following: (1) a limited array of targetable antigens and heterogeneous antigen expression; (2) limited T-cell fitness and survival before arriving at tumor sites; (3) inefficient homing to and penetration of solid tumors; and (4) a hostile, immunosuppressive tumor microenvironment.
Prioritizing and streamlining the clinical evaluation of proposed strategies for overcoming those roadblocks will be a key challenge going forward, researchers advised. Furthermore, specialists need to better understand basic CAR T-cell biology, as well as how cancer cells and immune cells interact with transferred CAR T-cells.
They suggested future CAR T-cell design would benefit from industrial designer Dieter Rams’ principles for good design.
Wagner J, Wickman E, DeRenzo C, Gottschalk S. CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality?. Mol Ther. 2020;28(11):2320-2339. doi:10.1016/j.ymthe.2020.09.015