Hey Wait, yes, Jean Campbell described some of the patent application's elements last fall, but didn't describe the formulated compositions in any detail.
Here is what I think is interesting about this application:
1. They are trying to maximize protein expression intratumorally by combining various encoded genes on a single plasmid.
2. They now include tumor associated antigens fused to adjuvants on the same plasmid. This will hypothetically allow for improvements in CD8 tcell activation and thus lead to stronger immune responses against tumor targets. Adaptive immune responses require recognition of non-self tumor antigens, i.e. neoantigens, to drive immunity. Having a tumor antigen fused to something like heat shock protein 96 will theoretically improve presentation to dendritic cells, which in turn present to t-cells for activation. They can also now evaluate the immune response by analyzing lymphocytes for the presence of the encoded antigens.
3. Being able to encode various proteins on a single plasmid is one of the first steps towards developing personalized immunotherapies. This is a possible plug and play in the making. Once you figure out the tumor profile of the patient, you can theoretically tailor the plasmid to contain specific antigens unique to the patient. This won't negate the need for checkpoint inhibitor treatments, but it will certainly drive the tumor infiltrating lymphocytes that need to exist before checkpoint inhibitor therapy. Having the expression promoters and fused adjuvants on the same plasmid should contribute to adequate immunity. Adequate protein expression has always been a challenge for electrogene transfer, but combining GENESIS with TRACE, encoded adjuvants, promoters, cytokines and tumor associated antigens is really loading the deck, and they are able to do it right where it's needed most - intratumorally. This will lead to a systemic immune response through the release of tumor specific antigens, i.e. neoantigens.
4. They seem to leave the door open to cassettes that contain RNA sequences. RNA doesn't need to make it to a cell nucleus to express a protein. See Moderna Therapeutics on the possible implications for this.
