Immune effects by selective heating of membrane rafts of cancer-cells.
ABSTRACT
Background: The immune stimuli by local selective excitation of membrane rafts of malignant cells may extend the local method to systemic effect (abscopal effect). Our objective is to study this process from local action to systemic result.
Methods: Impedance controlled RF current (modulated electro-hyperthermia, mEHT) is applied with time-fractal pattern modulated 13.56 MHz carrier frequency [1]. mEHT selectively targets the membrane raft domains of malignant cells [2]. We applied different murine tumor models (xenografts and allografts) to investigate the effects. The tumor samples were evaluated by various histomorphological and immunohistochemical methods using a digital microscopy technology to qualitatively and quantitatively evaluate the samples.
Results: mEHT induced massive apoptotic cell death in the treated tumors by caspase independent subroutine in HT29 colorectal adenocarcinoma xenografts [3]. This programmed cell death procedure has also shown a damage associated molecular pattern (DAMP) formation, which is a prerequisite of the immunogenic cell-death process (ICD) [4]. The abscopal effect was measured in C3H/He allograft mouse model in conjunction with intratumoral dendritic cell (DC) injection, [5]. In this model, not just the directly treated tumor but the distant untreated tumor lesions have also shown the signs of the effective damage. mEHT plus DC administration significantly inhibits the CT26 tumor growth in BALB/c mouse model, while even the re-challenging of the tumor inoculation became impossible [6].
Conclusions: mEHT induces DAMP associated ICD and creates a favorable tumor microenvironment for an immunological chain reaction that improves the success rate of intratumoral DC immunotherapy. The tumor specific immune reaction became abscopal effect and acted systemically despite the certainly local application of mEHT.
Reference [1] Szasz A et.al. Oncothermia, Springer, 2010 [2] Szasz O et.al J Clin Oncol 33, 2015 (suppl; abstr e22176) [3] Meggyeshazi N. et.al. Strahlenther Onkol, 190:815-822; 2014 [4] Andocs G. et.al. Cell Stress and Chaperones, 20:37-46; 2015 [5] Qin W et.al. Oncol Rep 32:2373-2379; 2014 [6] Tsang Y-W et al. BMC Cancer 15:708; 2015