Focused shock waves and inertial cavitation release tumor-associated antigens from renal cell carcinoma

Abstract

Tumor biomarkers play an essential role in immunotherapeutic strategies in cancer treatment, contributing to early diagnosis, patient selection, treatment monitoring, and personalized treatment plans. Despite their importance in cancer care, circulating biomarkers may not always be detectable or sufficiently elevated to provide reliable test results. Due to the pressing need for innovative approaches to enhance biomarker levels, this study explored the potential use of focused shock waves and cavitation for non-invasively releasing tumor-associated antigens. Renal carcinoma cell lines ACHN and TOS-1 were used in an in vitro study to analyze the impact of shock waves on two membrane glycosphingolipid antigens, MSGG and G1, respectively. Focused shock waves were generated using a partial spherical piezoceramic dish. Flow-cytometric analysis of treated cells immediately after 1,000 focused shock waves at 16 MPa overpressure showed a 29.4 % and 17.6 % decrease in MSGG and G1 antigens on the cell surfaces. In the immunostaining of glycosphingolipid fractions on thin-layer chromatography (TLC), both tumor markers were reduced by an average of 49.30 % (MSGG) and 57.08 % (G1). Immunoelectron microscopy images confirmed decrease in the cell membrane intensity immediately after shock waves because of the release of antigens into the extracellular spaces. The released antigens were primarily found on cell debris formed by shock waves and cavitation induced damage to the cell membrane. Theoretical analyses were performed to understand antigen release mechanisms. Moreover, the biophysical events that occurred following the interaction of a shock wave with a suspended cell were modeled and clarified. A novel model was used to calculate the tensile stresses following shock waves and to explain the deformations observed in scanning electron microscopy images. The release of tumor antigens by focused shock waves and inertial cavitation represents exciting prospects for advancing cancer care strategies.