OncoSec Medical Inc (ONCSQ)

[hschlauch]

Gene electrotransfer:

Genetic material (DNA) is trafficked to a cell nucleus after electroporation where the DNA is converted into RNA (transcription) and then the RNA is converted into, for example, functional proteins or molecules(translation). These proteins and molecules are the products that become EXPRESSED TO FUNCTION OUTSIDE THE CELL.

Electroporated genetic constructs of cytokines, antigens, toll-like receptors, antigen chaperones, co-stimulatory molecules, chemokines, and monoclonal antibodies can all go through this same "manufacturing" process.

And yes, you can have tumor cells express the phenotypes for encoded monoclonal antibodies like anti-pd-1, anti-ctla-4, anti-tim-3, etc. Efficiency, robust and lasting expression, safety, and reliability are all reasons for electroporating monoclonal antibody-encoded DNA plasmids, ie checkpoint inhibitors, in tumors. This is where you find the antigen-specific tumor infiltrating lymphocytes (TIL)that up-regulate pd-1 on their cell surface in the presence of interferon gamma, owing to the IL-12. Guess what else then gets up-regulated? Yep, pdl1 on tumor cells. When you have both the pdl1 (ligands) on tumor cells and the pd-1 on antigen specific TIL up-regulated you get a stalemate. That is when you unleash the checkpoint inhibitors to allow the TIL to do their job of killing tumor cells.