Alpha-Emitters Radiation Therapy and PSMA-targeting-therapy as a combination modality for prostate cancer
2Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Israel
Prostate cancer (PCa) is the second most common cancer in male patients after lung cancer and is the fifth leading cause of cancer-related death worldwide. In the advanced stages of the disease, radiation therapy may be applied to reduce tumor growth. We developed a unique internal irradiation technique called Diffusing Alpha-Emitters Radiation Therapy (DaRT), enabling the treatment of solid tumors using dispersed alpha-emitting atoms. However, potential ‘cold spots’ in the periphery of treated tumors might cause relapse due to incomplete coverage of the entire tumor tissue. To target such ‘cold spots’, we used the highly potent camelid-derived nanobody (NB) that was previously engineered to target prostate-specific membrane antigen (PSMA), transmembrane receptor overexpressed on the surface of PCa cells. Due to its specificity to the PCa cells, PSMA can be exploited for the delivery of chemotherapeutic agents such as Doxorubicin (DOX). In this project, we generated an NB-DOX conjugate (designated NB-DOX), which showed binding and internalization specifically to PCa cells that overexpress PSMA (PC3-PIP cells) and efficiently reduced their viability. In addition, our preliminary results indicate that DaRT inhibits the growth of tumor cells, both in vitro and in vivo; the average size of DaRT-treated tumors was smaller than the control groups both in PC3-PIP (PSMA+) and PC3-FLU (PSMA-) mice. Next, we will test our hypothesis that the combination of DaRT and NB-DOX will achieve a complete tumor coverage and yield a significantly better tumor eradication outcome, thus becoming beneficial as a novel modality for the treatment of PCa.