Breast cancer is one of the most common cancer types in women and its metastases cause most patient deaths in the advanced stage of this disease. 1,2,3 Unfortunately, metastases develop drug resistance to chemotherapy and impaired T lymphocyte infiltration into metastatic lesions by compressing blood vessels. 4,5,10,11,12 Although losartan decompressed vessels and increased the presence of T lymphocytes in the metastatic lesions, T-cells were not effective at eliminating tumors.10 In this thesis, we generated chimeric antigen receptor constructs that have specificity against epithelial cell adhesion molecule (EpCAM). After optimizing a retroviral transfection/transduction system, we successfully generated EpCAM CAR T-cells and tested their efficacy against tumor spheroids. We noticed a dramatic reduction of spheroids' area and spheroids' diameter after 36 hours of treatment and observed spheroids’ destruction and tumor cell elimination after 96 hours of treatment, compared to non-specific stimulated T-cells treatment on tumor spheroids. EpCAM CAR T-cells have been shown to be effective against cancer in vitro; therefore, injection of EpCAM CAR T-cells into mice with breast cancer will be conducted to determine whether losartan is able to improve infiltration. We expect that the use of losartan will improve the number of infiltrated CAR-T-cells and their efficacy against breast tumors.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/48404 |
| Date | 14 March 2024 |
| Creators | Wang, Zixiong |
| Contributors | Jones, Dennis, Duffy, Elizabeth R. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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