About this Research Topic
Recent advances in phase I trials for solid tumors, as well as in pre-clinical models, have revealed several variables that will be important to consider for the successful use of CAR-T cells in treating solid tumors. These variables include (i) regional versus systemic delivery; (ii) scFv versus ligand interactions; (iii) antigen loss versus escape; (iv) epitope spreading and (v) checkpoint expression on immune cells or tumor cells. Also, there remains outstanding mechanistic questions related to why differences exist in the persistence and tonic signaling of second-generation CD28 versus 4-1BB co-stimulated CAR-T cells. In addition, we are now learning the roles of lympho-depleting regimens (and associated toxicities) in modifying the persistence of engineered T cell therapies.
A more comprehensive view of CAR-T cell strategies and important advances, both of pre-clinical and clinical evaluations, in solid tumors is necessary to drive these therapies forward.
Therefore, in this Research Topic we welcome the submission of Reviews, Mini-Reviews, Case Reports and Clinical Trial articles:
1. Evolving understanding of the molecular signaling of CAR-T cells, the differences that exist between varied second-generation CARs, and the interaction of CARs, if any, with the TCR complex.
2. Strategies for improving T cell persistence and/or homing to tumor sites.
3. Predictive biomarker analysis within patient populations or within cell populations for improved CAR-T cell potency.
4. Emerging approaches to overcome tumor and milieu immunosuppression.
5. Co-evaluation of cellular product administration routes for persistence, homing, and efficacy.
6. Gene editing and engineering of allogeneic cells for universal CAR-T (UCAR-T) cell development, including methods to increase persistence of UCAR-Ts.
Keywords: CAR- T cells, CAR-T cell therapy, Solid Cancer
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.