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Re: trading.jeff post# 37969

Wednesday, 01/04/2017 2:11:10 PM

Wednesday, January 04, 2017 2:11:10 PM

Post# of 48316
This is an interesting combination plug-and-play approach using patient-specific neoantigens with checkpoint inhibitors.

Another plug-and-play could be obtaining the tumor neoantigens through sampling, characterizing them through bioinformatics, and using a plug-and-play electrogene transfer method (electroporation) with other genetic constructs (e.g. IL-12) on plasmids delivered intratumorally.

Alternatively, you can create an in-situ vaccine targeting tumor neoantigens that won't require tumor sampling. What you need is a mechanism to get tumor cells to expose their neoantigens (e.g. through tumor cell death), professional antigen presenting cells (vis-a-vis IL-12) e.g. dendritic cells, co-stimulatory molecules (e.g. OX40L) for t-cell clonality, and upregulation of checkpoints like PD-1 and CTLA-4 on activated CD8 "killer" t-cells and tumor cells (vis-a-vis interferon gamma production by IL-12). All of these pathways can be triggered by the expression of DNA constructs delivered intratumorally through electroporation. This sets the stage for checkpoint inhibitors like anti-PD-1 and anti-CTLA-4 drugs. Robert Pierce is all over this streamlined in-situ vaccine approach.