Wednesday, December 07, 2016 12:58:36 PM
Some researchers are approaching personalized therapies through the identification of tumor associated antigens, i.e. neoantigens, that allow tumor cells to be recognized by the immune system. For some, the question is which prediction software will be most precise in identifying the tumor cell antigens found in each patient's tumors. For example, see Parker Institute for Cancer Immunotherapy and Cancer Research Institute Launch Collaboration on Cancer Neoantigens
at http://www.cancerresearch.org/news/2016/pici-and-cri-launch-collaboration-on-cancer-neoantigens#sthash.Hl7W8YCT.dpuf
This approach requires sampling individual tumors' DNA to identify neoantigens. I think once they nail down the best predictive software, this could hypothetically lead to a "plug-and-play" administration of matching antigens, that is a personalized vaccine. This "plug-and-play" approach to personalized therapies was mentioned by RP last month. If you know each individual's tumor neoantigens, and you can create a personalized vaccine, do you administer the vaccine intratumorally or systemically? In my non-professional opinion, it would make more sense to send the vaccine directly to where it needs to be applied - the tumor from which the neoantigens originate.
Now what happens when you have matching antigens already prepared in the form of DNA plasmids, which you could combine and deliver via electro transfer soon after identifying each individual's tumor neoantigens? Vaccines have a reputation for eliciting mediocre immune responses without adjuvants. So, you combine the DNA plasmid vaccine with DNA constructs of IL-12 and other agents to optimize CD8 tcell activation in the tumor microenvironment where the neoantigens originated. In case you missed it, last month Jean Campbell also discussed how the next gene product is going to use a polycistronic cassette that may incorporate personalized antigens (neo-antigens).
You can take an in-situ approach as well that takes advantage of antigen chaperones like Heat Biologics GP96-lg in the form of DNA plasmids. This too is a personalized therapy that allows neoantigens to be transported by antigen presenting cells, e.g. dendritic cells, leading to CD8 t-cell activation. The GP96-lg "chaperones" individual tumor cells' antigens to the antigen presenting cells. Once again combine this with DNA plasmids expressing synergistic molecules like IL-12 and OX40L.
Therefore, there are two distinct intratumoral vaccine approaches that could be maximized by Oncosec's Genesis. There are quite frankly no gene electro transfer devices other than Oncosec's that conforms to tissue conditions for optimal delivery of DNA plasmids; it can be used with any tumor type. And, at least in my opinion, there is no better way to deliver a targeted(ex vivo developed) personalized vaccine than to do it directly in the tumor from which the neoantigens were removed.
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