Chimeric Antigen Receptor-modified T Cells Repressed Solid Tumors and Their Relapse in an Established Patient-derived Colon Carcinoma Xenograft Model.

Adoptive transfer of T cells engineered with a chimeric antigen receptor (CAR) is deemed as the silver bullet to overcome the barriers of solid tumor treatment; however, the therapeutic application against solid tumors faces major challenges largely owing to the complex heterogeneity and immunosuppressive microenvironment of solid tumors. Preclinical development of CAR-T-cell products necessitates an appropriate animal model for the evaluation and improvement of their therapeutic capacities. Patient-derived xenograft (PDX) resembles real patients in several ways, and may serve as an attractive alternative to generate and evaluate the efficacy of CAR-T-cell products. In this study, we established and characterized a PDX mouse model implanted with colorectal cancer (CRC) xenograft. Human epidermal growth factor receptor 2 (HER2) expression in CRC specimens was detected by immunohistochemistry. The fragments of patient tumors were subcutaneously implanted into immunodeficient NOD-NPG mice after surgery. Furthermore, HER2-specific CAR-T cells were engineered and tested in our model to show their effectiveness in tumor clearance. Adoptive transfer of HER2-specific CAR-T cells resulted in the regression or even elimination of CRC xenograft and protection of relapse from rechallenged colon cancer tissue in PDX model. Significant survival advantage was achieved in these mice as compared with those transplanted with green fluorescent protein-T cells. Thus, this study showed that CAR-T-cell treatment may be a promising approach for solid tumor clearance and that the PDX model may be useful to evaluate the effects of CAR-T cells.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. https://creativecommons.org/licenses/by-nc-nd/4.0/.