Anti-tumour effect of the fourth-generation chimeric antigen receptor T cells targeting CD133 against cholangiocarcinoma cells

• Published in: International immunopharmacology 2020-12, Vol.89, p.107069-107069, Article 107069
• Main Authors: Sangsuwannukul, Thanich, Supimon, Kamonlapat, Sujjitjoon, Jatuporn, Phanthaphol, Nattaporn, Chieochansin, Thaweesak, Poungvarin, Naravat, Wongkham, Sopit, Junking, Mutita, Yenchitsomanus, Pa-thai
• Format: Article
• Language: English
• Subjects: Adoptive T cell therapy; Anticancer properties; Antigens; Bile ducts; Cancer; Cancer stem cell; CAR T cell; CD133; CD133 antigen; Chimeric antigen receptor; Chimeric antigen receptors; Cholangiocarcinoma; Clinical trials; Health services; In vivo methods and tests; Lymphocytes; Lymphocytes T; Lysis; Receptors; Stem cells; Tumor necrosis factor-α; Tumors; γ-Interferon
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.107069

•CD133 expression in patient tissues and cholangiocarcinoma (CCA) cells were shown.•Anti-CD133 CAR4 T cells containing CD28/CD137/CD27/CD3ς was successfully created.•The concept of using anti-CD133 CAR4 T cells against CD133+ CCA cells is proved.•Anti-CD133 CAR4 T cells is a potential cancer immunotherapy for CCA treatment. Current treatment of cholangiocarcinoma (CCA) – a lethal bile duct cancer – is ineffective because the disease is usually diagnosed at late and advanced stage. Thus, a novel therapeutic modality is urgently required. Fourth-generation chimeric antigen receptor (CAR4) T cells was created to target CD133, a well-known cancer stem cell marker, that is highly expressed and associates with cancer progression. The anti-CD133-CAR4 T cells showed high efficacy against CD133-expressing CCA cells. Tumour cell lysis occurred in a dose- and CD133 antigen-dependent manner, and significantly higher, up to 57.59% ± 9.62 at effector to target ratio of 5:1 in a CCA cell line – KKU-213A cells, compared to mock control (p = 0.008). Similarly, significant IFN-γ (p = 0.011) and TNF-α (p = 0.002) upregulation was observed upon tumour treatment. The effectiveness of our anti-CD133-CAR4 T cells will be beneficial not only for CD133-expressing CCA, but also for other CD133-expressing tumours. This study may guide future in vivo study and clinical trials.