Anti-CD19 CAR-T cell therapy(Juno Therapeutics, Inc.)

Triple-negative breast cancer (TNBC) is an aggressive cancer subtype for which effective therapies are lacking. Epidermal growth factor receptor (EGFR) is overexpressed in various types of TNBC cells, and several EGFR-specific immunotherapies have been used to treat cancer patients. Chimeric antigen receptor engineered T (CAR-T) cells have also been used as cancer therapies. In this study, we generated two types of EGFR-specific CAR-modified T cells using lentiviral vectors with DNA sequences encoding the scFv regions of two anti-EGFR antibodies. The cytotoxic and antitumor effects of these CAR-modified T cells were examined in cytokine release and cytotoxicity assays in vitro and in tumor growth assays in TNBC cell line- and patient-derived xenograft mouse models. Both types of EGFR-specific CAR-T cells were activated by high-EGFR-expressing TNBC cells and specifically triggered TNBC cell lysis in vitro. Additionally, the CAR-T cells inhibited growth of cell-line- and patient-derived xenograft TNBC tumors in mice. These results suggest that EGFR-specific CAR-T cells might be a promising therapeutic strategy in patients with high-EGFR-expressing TNBC.

NK cells may have great potential in tumor immunotherapy because they can kill tumor cells directly and quickly. Chimeric antigen receptor is a fusion protein composed of extracellular antigen recognition domain, transmembrane domain and intracellular signal domain. Rapid development of CAR-modified T cells has made tremendous achievements in the treatment of malignancies, especially hematological malignancies. However, there are many deficiencies in clinical application of CAR-T cell therapy. Car-modified NK cells have attracted much attention because they may avoid these shortcomings. At present, preclinical and clinical studies have shown that CAR-NK cell therapy may play significant anti-tumor role and it is safer than CAR-T cell therapy. Nevertheless, CAR-NK cell therapy still faces some challenges, such as the expansion and activation of primary NK cells in vitro, the difficulty to store and ship NK cell products and the low transduction efficiency. Thus further research is still needed to optimize CAR-NK cell therapy. Building better CAR-NK cells is important to improve the treatment efficacy and combination therapy offers a novel direction of NK-cell based immunotherapy.