%A Long,Kristen B. %A Young,Regina M. %A Boesteanu,Alina C. %A Davis,Megan M. %A Melenhorst,J. Joseph %A Lacey,Simon F. %A DeGaramo,David A. %A Levine,Bruce L. %A Fraietta,Joseph A. %D 2018 %J Frontiers in Immunology %C %F %G English %K CAR (chimeric antigen receptor) T cells,Immunothearpy,Cancer,Solid tumor,Microenviroment,adoptive cell therapy,Non-hematopoietic neoplasm %Q %R 10.3389/fimmu.2018.02740 %W %L %M %P %7 %8 2018-December-03 %9 Review %# %! CAR T cells for non-hematopoietic malignancies %* %< %T CAR T Cell Therapy of Non-hematopoietic Malignancies: Detours on the Road to Clinical Success %U https://www.frontiersin.org/articles/10.3389/fimmu.2018.02740 %V 9 %0 JOURNAL ARTICLE %@ 1664-3224 %X Chimeric antigen receptor (CAR)-engineered T cells represent a breakthrough in personalized medicine. In this strategy, a patient's own T lymphocytes are genetically reprogrammed to encode a synthetic receptor that binds a tumor antigen, allowing T cells to recognize and kill antigen-expressing cancer cells. As a result of complete and durable responses in individuals who are refractory to standard of care therapy, CAR T cells directed against the CD19 protein have been granted United States Food and Drug Administration (FDA) approval as a therapy for treatment of pediatric and young adult acute lymphoblastic leukemia and diffuse large B cell lymphoma. Human trials of CAR T cells targeting CD19 or B cell maturation antigen in multiple myeloma have also reported early successes. However, a clear and consistently reproducible demonstration of the clinical efficacy of CAR T cells in the setting of solid tumors has not been reported to date. Here, we review the history and status of CAR T cell therapy for solid tumors, potential T cell-intrinsic determinants of response and resistance as well as extrinsic obstacles to the success of this approach for much more prevalent non-hematopoietic malignancies. In addition, we summarize recent strategies and innovations that aim to augment the potency of CAR T cells in the face of multiple immunosuppressive barriers operative within the solid tumor microenvironment. Advances in the field of CAR T cell biology over the coming years in the areas of safety, reliability and efficacy against non-hematopoietic cancers will ultimately determine how transformative adoptive T cell therapy will be in the broader battle against cancer.