OncoSec Medical Inc (ONCSQ)

[hschlauch]

Thanks for taking the time to read and respond to my comments. I'm not a medical professional, just someone who is genuinely interested in cancer research, so I appreciate your input.

I tend to think that the use of antigen chaperones (GP96) in the context of an inflamed tumor microenvironment (driven primarily by interferon gamma through IL-12) will allow for improved activation of CD8 t-cells that can target tumor-specific (neo)antigens. The antigen chaperones would actively deliver neoantigens to antigen presenting cells, which should be prolific in the context of an inflamed tumor microenvironment. This, the activation of neoantigen-specific CD8 t-cells, I think would drive the exhausted pd-1/ctla-4-positive TIL phenotype. When a co-stimulatory molecule like OX40L is added to the mix, there should theoretically be a polyclonal expansion of the differentiated CD8 t-cells along with improvements in memory precursor cells.

The exhausted TIL phenotypes (pd-1 and ctla-4) are an apparently essential requirement for checkpoint inhibitor efficacy. If true, then a local expression of checkpoint inhibitors, manufactured over the course of several days by tumor cell machinery vis-a-vis EP genes, should not only release the brakes on blocked TIL, but should also continuously feed TIL and augment tumor cell destruction due to the TIL phenotype expressions present. This could potentially lead to a positive feedback loop in which more neoantigens are released and more inflammatory cytokines are produced in the immediate tumor environment, thus leading to a significant systemic immune response.

Again, there is no indication that the company will go down this road, but the synergy between all of these EP agents is screaming, at least to me.