Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 89, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2020.107069
Keywords
Adoptive T cell therapy; Chimeric antigen receptor; CAR T cell; CD133; Cancer stem cell; Cholangiocarcinoma
Categories
Funding
- Siriraj Research Fund of the Faculty of Medicine Siriraj Hospital, Mahidol University [R016034008]
- Mahidol University [R015810005]
- Thailand Research Fund (TRF) [IRG5980006]
- International Research Network, Thailand [IRN58W0001, IRN5801PHDW02, IRN5801PHDW04]
- Siriraj Chalermphrakiat Grants
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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-gamma (p = 0.011) and TNF-alpha (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.
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