Just so I don't divert much from an ONCS discussion, I will say this: both PPHM and ONCS hope to achieve similar goals, i.e. expanding the number of TIL to allow for a more robust response to checkpoint inhibitor therapies.
PPHM has what appears to be some good things going for it judging by response data in preclinical trials.
I do believe their combinations with chemotherapy agents are going to be hindrances in terms of duration of responses though, and there are a lot of these investigator-led trials with chemo agents. Most chemo agents suppress the adaptive immune system, thus giving rise to recurrences and only partial responses. You can see that in the phase 1 bavi-plus-pacli her2-negative breast cancer study: response durations drop like a rock.
It is also starting to look like combination monoclonal antibodies, i.e. checkpoint inhibitors, may give rise to decent partial responses, e.g see yervoy and opdivo, but their systemic application is leading to terrible SAEs. That would be my primary concern with bavi use in combination with other mabs. You see some good preclinical responses, but will they prove to be risky relative to another treatment accomplishing similar efficacy? Because they are administered systemically, that means they could be releasing the brakes throughout the body wherever the checkpoints exist, not just in tumor microenvironments.
Also, the way we should probably view immunopulse EP IL-12 is as an in-situ vaccine that is capable of driving a significant immune response primarily through the production of interferon gamma. Triggering interferon gamma in the tumor microenvironment draws the attention of antigen presenting cells to tumor-specific antigens. Once APC take these antigens to naive t cells, the tcells become activated as CD8 killer tcells. This is the basic mechanism that leads to innate immune responses and the abscopal effect.
Because the primary function of IL-12 is to stimulate the immune system indirectly through interferon gamma production, it makes a lot of sense to electroporate it within the tumor prior to using checkpoint inhibitors. As a corrolary to the innate immune response with neoantigen matching, there should theoretically be significant response durations observed with EP IL-12. In addition, because PD-1 positive immune cells are by far the most common checkpoints in exhausted TIL, it makes more sense to target just that checkpoint over others if adding additional mabs leads to systemic toxicities. Lets see what they can accomplish by just combining EP IL-12 with an anti-PD-1.
AI
