High-Throughput Flow Cytometric Method for the Simultaneous Measurement of CAR-T Cell Characterization and Cytotoxicity against Solid Tumor Cell Lines.
Chimeric antigen receptor-modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors.
CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity.
In this review, we discuss the structure of the CAR, current clinical advantages from finished and ongoing trials, adverse effects, challenges and controversies, new engineering methods of CAR, and clinical considerations that are associated with CAR T cell therapy both in hematological malignancies and solid tumors.
New regimens, including combinations with chemical drugs, need to be studied to enhance the therapeutic efficacy of CAR-T or NK cells for solid tumors.
The obstacles that reduce the efficacy of CAR-T therapy in solid tumors include a lack of specific tumor antigens, limited trafficking and penetration of CAR-T cells to tumor sites, and an immunosuppressive tumor microenvironment.
These adjuvant-like effects of GSK3 inhibition on activated CAR-T cells may be a valuable adjunct to a successful implementation of CAR-T immunotherapy against GBM and other solid tumors.
CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials.
Specifically, this review covered the following areas: (1) the current status of CAR-T cells in the treatment of solid tumors; (2) the major factors constraining the efficacy of CAR-T cells in solid tumors; and (3) opinions regarding the future of CAR-T as a treatment for solid tumors.
Overall, our data document the superiority of local production of PD-L1 mini-body by CAd-VEC<i>PDL1</i> combined with administration of tumor-directed CAR T cells to control the growth of solid tumors.<i></i>.
Whereas much of the early success with CAR-T cells has been demonstrated with hematological malignancies, important barriers remain for the application of CAR-T cell therapies for the management of metastatic solid tumors.
Two preclinical studies indicate the potential of using biodegradable nanoparticles to program circulating T cells into CAR T cells <i>in situ</i>, and delivering these therapeutic cells directly to solid tumors via small dissolvable sponges.
Chimeric antigen receptor T (CAR-T) cells have shown promising efficacy in treatment of hematological malignancies, but its applications in solid tumors need further exploration.
This strategy may facilitate the application of immunotherapy to solid tumors by affording comparable efficacy with improved safety owing to switch-based control of the CAR-T response.