| Autor: |
Falk H; Center for Experimental Drug and Gene Electrotransfer (CEDGE), Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev Ringvej, Herlev, Denmark., Forde PF; Cork Cancer Research Center, Western Gateway Building, University College Cork, Western road, Cork, Ireland., Bay ML; Centre of Physical Activity Research, Center of Inflammation and Metabolism, Copenhagen University Hospital, Blegdamsvej, København, Denmark., Mangalanathan UM; Center for Experimental Drug and Gene Electrotransfer (CEDGE), Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev Ringvej, Herlev, Denmark., Hojman P; Centre of Physical Activity Research, Center of Inflammation and Metabolism, Copenhagen University Hospital, Blegdamsvej, København, Denmark., Soden DM; Cork Cancer Research Center, Western Gateway Building, University College Cork, Western road, Cork, Ireland., Gehl J; Center for Experimental Drug and Gene Electrotransfer (CEDGE), Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev Ringvej, Herlev, Denmark. |
| Abstrakt: |
Electroporation is used in cancer treatment because of its ability to increase local cytotoxicity of e.g. bleomycin (electrochemotherapy) and calcium (calcium electroporation). Calcium electroporation is a novel anticancer treatment that selectively kills cancer cells by necrosis, a cell death pathway that stimulates the immune system due to high release of antigens and "danger signals." In this exploratory study, we aimed to investigate whether calcium electroporation could initiate an anticancer immune response similar to electrochemotherapy. To this end, we treated immunocompetent balb/c mice with CT26 colon tumors with calcium electroporation, electrochemotherapy, or ultrasound-based delivery of calcium or bleomycin. High treatment efficiency was observed with 100% complete remission in all four groups (12/12 with complete remission in each treatment group). In addition, none of the surviving mice from these groups formed new tumors when re-challenged with CT26 cancer cells 100-d post treatment, whereas mice challenged with different cancer cells (4T1 breast cancer) all developed tumors. Treatment of immunodeficient mice with calcium electroporation and electrochemotherapy showed no long-lasting tumor response. Calcium electroporation and electrochemotherapy was associated with a release of High Mobility Group Box 1 protein (HMGB1) in vitro ( p = 0.029) and a significant increase of the overall systemic level of pro-inflammatory cytokines in serum from the treated mice ( p < 0.003). These findings indicate that calcium electroporation as well as electrochemotherapy could have a role as immune stimulators in future treatments. |
