Abstract
Background Triple-negative breast cancer (TNBC) is the worst prognosis subtype of breast cancer due to lack of specific targets. Recent studies have shown that immunotherapy may solve that problem by targeting folate receptor-alpha (FRα). Methods Gene modified γδ T cells were manufactured to express FRa specific chimeric antigen receptor (FRa CAR) and secrete interleukin-7 (IL-7) and chemokine C–C motif ligand 19 (CCL19). CAR-γδT cells that secrete IL-7 and CCL19 (7 × 19 CAR-γδT) were evaluated for their antitumor activity both in vitro and in vivo. Results 7 × 19 CAR-γδT showed remarkable antitumor activity in vitro. Combined with PBMC, 7 × 19 CAR-γδT inhibited TNBC xenograft model growth superiorly compared with single-application or conventional CAR-γδT cells. Histopathological analyses showed increased DC or T cells infiltration to tumor tissues. Conclusion Taken together, our results showed that 7 × 19 CAR-γδT have remarkable anti-TNBC tumor activity and showed a broad application prospect in the treatment of incurable TNBC patients.
Highlights
Triple-negative breast cancer (TNBC) is a kind of deadly disease, and there are nearly 15% of invasive breast cancer are TNBC [1]. e expression of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) is negative in TNBC patients.us, endocrinotherapy and HER-2 targeted therapy were ineffective when treating TNBC, which necessitates novel treatment methods for TNBC patients
The treatment effect of second and third generation Chimeric antigen receptor (CAR)-Tcells is still controversial [3]. ere are still many obstacles to overcome in the application of CAR-T cell therapy fighting against solid tumor
Our results demonstrated that the 7 × 19 CARcδT cell can strongly suppress TNBC tumor in vivo through various mechanisms
Summary
Us, endocrinotherapy and HER-2 targeted therapy were ineffective when treating TNBC, which necessitates novel treatment methods for TNBC patients. Chimeric antigen receptor (CAR) T cell had shown brilliant antitumor ability in hematologic malignancy by targeting the certain antigen such as CD19 and CD20 [2]. Ere are still many obstacles to overcome in the application of CAR-T cell therapy fighting against solid tumor. Triple-negative breast cancer (TNBC) is the worst prognosis subtype of breast cancer due to lack of specific targets. CAR-cδT cells that secrete IL-7 and CCL19 (7 × 19 CAR-cδT) were evaluated for their antitumor activity both in vitro and in vivo. 7 × 19 CAR-cδT showed remarkable antitumor activity in vitro. Our results showed that 7 × 19 CAR-cδT have remarkable anti-TNBC tumor activity and showed a broad application prospect in the treatment of incurable TNBC patients
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