Prostate cancer is the most common cancer in men and the third leading cause of cancer-related deaths in Canadian men. Despite hormone and radiation therapies, most patients progress to late-stage metastatic castrate-resistant prostate cancer (mCRPC). 177Lu-PSMA617 radioligand therapy (rLT) is a radioactive biochemical substance that targets the human prostate-specific membrane antigen (hPSMA). This rLT has been used in compassionate trials in mCRPC patients and has been demonstrated significant clinical efficacy. However, recent findings suggest that this efficacy is short-lived, and most patients exhibit tumor recurrence [96]. Here we establish a murine model to study the anti-tumor effects and the corresponding immune response of 177Lu-PSMA617 rLT on prostate cancer. We generated a doxycycline-inducible hPSMA-expressing murine prostate cancer (hPSMA TRAMP-C2) cell line with high binding responses to PSMA617. Using this system, we evaluated the in vitro and in vivo binding of 177Lu-PSMA617 to the hPSMA TRAMP-C2 cell line. Here, we show that the hPSMA TRAMP-C2 cell line expresses hPSMA upon doxycycline induction and that 177Lu-PSMA617 can bind to its target in vitro and in vivo. Together, these results show that the developed hPSMA TRAMP-C2 cell line can be used to investigate therapeutic and immunological responses targeted against PSMA in prostate cancer. / Graduate
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/12479 |
| Date | 21 December 2020 |
| Creators | Joshi, Jay |
| Contributors | Lum, Julian J. |
| Source Sets | University of Victoria |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
| Rights | Available to the World Wide Web |
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