Has anyone noticed how nearly every single partial responder - it might even end up being every responder over a few more months - to the phase 2 combination ends up being a complete responder! Swimmer plots illustrate these conversions. The updated data showed 9 out of 22 patients being complete responders.
None of these treated patients who obtained a response ever actually progressed - that speaks to the robust tumor antigen-specific, i.e. neoantigen, immune response. That probably would not have been possible if IL-12 was not expressed sufficiently intratumorally. IL-12 stimulates the production of interferon gamma by T helper cells. In turn, this increases the activity of antigen presenting cells, which produce even more IL-12, thus driving significant tumor-specific immune responses. This creates a positive feedback loop intratumorally and improves the odds of neoantigen presentation - the reason it is being called an in situ vaccine platform. In theory, every single tumor antigen can be presented, and you radically improve the odds of a response when you have more macrophages present intratumorally.
In addition, the corollary immune cells that result from interferon gamma production are the partially exhausted phenotypes. In the presence of interferon gamma, PD-1 becomes unregulated by T cells and tumor cells respond by upregulating PD-1 ligands. This is where anti-PD-1 checkpoint inhibitors come into play. Without the pre-existing partially exhausted T cells present, you wouldn't get responses from anti-PD-1 drugs.
It looks like Oncosec might even be using a P2A-linked IL-12-encoded construct as a backbone to its upcoming multigene platform. If you aren't familiar with the P2A-linked gene, you should investigate how its expression compares to the current IRES structure.
