Lowe, I could be wrong, but your statement leads me to believe that you are misinterpreting ONCS's electroporated DNA-based therapy.
Yes, the genes go INTO cells, in this case tumor cells, but the genes are then processed and EXPRESSED as interleukins, antibodies, antigen chaperones, etc. The genes don't just stay in the cells as your post implies. The key advantage to electroporation is localized expression and safety mitigation. The expressed genes would then work either directly or indirectly on their targets through multiple pathways.
To drive a significant abscopal effect and immune response to cancer tumor cells, you would need recognition of neoantigens. Systemically administered checkpoint inhibitors are ultimately delivered to locations all over the body. This route of administration not only leads to severe toxicities when used in combination with other checkpoint inhibitors, but the effect is non-localized. In theory, or at least in my mind, electroporating checkpoint inhibitors would drive more significant localized tumor regressions in a shorter amount of time than systemic injections. In addition, you would see far fewer severe adverse events versus combination checkpoint inhibitors administered systemically. Electroporating an anti-pd-1, anti-ctla-4, etc monoclonal antibody (checkpoint inhibitor) with IL-12/GP96/OX40L would drive a profound immune response and abscopal effect because greater numbers of neoantigens would initially become exposed in the context of an inflamed tumor microenvironment. Metastatic lesions would then be subject to TIL with tumor specific neoantigens. There would theoretically still be a need for systemic applications of checkpoint inhibitors in some metastatic situations, but the electroporation of checkpoint inhibitor genes would substantially eliminate systemically delivered checkpoint inhibitors.
Electroporating DNA for checkpoint inhibitors with IL-12, GP96, and OX40L would 1) speed up neoantigen release and presentation to naive t-cells; 2) provide robust and continuous localized expression for perhaps up to a couple weeks; 3) lead to a profound abscopal effect and important innate immunity; and 4) provide a safer alternative to repetitive systemic checkpoint inhibitor use.
These are only my thoughts.
