GENERATION OF CHIMERIC ANTIGEN RECEPTOR T CELLS TARGETING MUCIN 1 AGAINST CHOLANGIOCARCINOMA
Cholangiocarcinoma (CCA) is a fetal malignancy of bile duct epithelial cells with poor prognosis and treatment outcome. It is a rare disease worldwide but frequent in the northeast of Thailand. Standard treatments are not effective in the advanced stage of CCA, leading to high recurrence rate, low prolong-survival, and chemo-resistance in the patients. Therefore, a novel therapy for CCA is needed. Chimeric antigen receptor (CAR) T cells have emerged as a new modality for cancer therapy with high efficacy. These cells recognize specific cancer antigen and induce cancer cell lysis. One of cancer-associated antigens, Mucin 1 (MUC1), is highly expressed in CCA tissue related to cancer progression. The cancer-associated MUC1 is hypoglycosylated when it is compared to heavy glycosylation in normal cells. MUC1-targeted CAR T cells have recently been studied in several cancer models; however, none of them have been used in CCA. Thus, this study aims to investigate anti-tumor efficacy of MUC1-targeted CAR T cells against CCA.
Initially, MUC1 expression was confirmed in CCA cells by Western blotting technique and flow cytometry. Then, anti-MUC1-CAR T cells were generated by using lentiviral vector system. These anti-MUC1-CAR T cells were evaluated for CAR expression and anti-tumor efficacy against CCA cells in vitro.
We found expression of MUC1 in CCA cells, suggesting that MUC1 can be used as an antigen for targeting CCA. The anti-MUC1-CAR T cells were generated by lentivirus transduction. These anti-MUC1-CAR T cells showed high efficiency of CCA cell lysis in highly expressed MUC1 as detected by luciferase assay.
This study showed that anti-MUC1-CAR T cells against MUC1 are potential to be further developed for CCA therapy.