ENPP1:

A breakthrough scientific discovery.

Science has made a recent breakthrough discovery: cancers not only upregulate the checkpoints (PD-1, PD-L1, others) to block adaptive immunity, they also upregulate ENPP1 to block innate immunity.

These are pro-cancerous proteins that suppress the immune system to help the cancer. For example, checkpoints suppress your T-cells and antibodies, so the cancer can grow without being attacked by your immune system. And Cancers upregulate ENPP1 so T-cells and antibodies do not “see” the cancer, so interferon will not attack it, and even so ENPP1 can help the cancer recover from chemotherapy treatment.

Adaptive Immunity is the half of your immune system that uses T-cells and antibodies to fight all the foreign things that bombard our systems every day – viruses, bacteria, parasites and cancer. And 99% of the time, our immune system takes care of all those bad guys. But occasionally one gets through, and this is the same with cancer.

The checkpoints are immune-suppressive proteins like PD1 and PDL1. They block the ability of adaptive immunity to fight the cancer. The immune-suppressive protein ENPP1 blocks innate immunity – As a result, adaptive immunity can’t see the cancer, your T-cells and antibodies don’t attack, and the cancer grows. This is why it is so important to add innate immunity into the fight. Blocking ENPP1 frees innate immunity like using checkpoint inhibitors frees adaptive immunity. Checkpoint inhibitors have been a revolutionary approach to fighting cancer. However, cancer develops resistance to checkpoint inhibitors, and still, they don’t “see” many cancers so using them alone is like fighting with one hand tied behind you back. We need to bring Innate Immunity into the fight and add an ENPP1 inhibitor.

Poster:

Preclinical studies of SR-8314, a highly selective ENPP1 inhibitor and an activator of STING pathway.

Innate Immunity is the second half of the immune system built into every cell – it “surveils” for foreign pathogens and is the first responder that inflames the cell to fight back. If you wonder why some cells in the human body sometimes becomes inflamed, it’s because of innate immunity. When it finds something wrong like cancer, it inflames that cell with interferon as a first responder defense.

But cancer secretes another protein — called ENPP1 — that helps cancer evade T-cells and antibodies and build resistance, even recover from chemotherapy. Defeating ENPP1 is our goal. It’s a revolutionary new approach that enables the full, two-fisted immune system (adaptive and innate) to work together to stop cancer.

Headquarters:

Texas Medical Center 2450 Holcombe Blvd., Suite X Houston, TX 77021 Jon@stingraytx.com

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