Deep-Priming™ Technology Platform

Our Deep-Priming platform is based on more than 10 years of research and development focused on taking very potent immunomodulatory drugs—cytokines, antibodies, and small molecules—that have the ability to activate and protect T cells from the “hostile” tumor microenvironment. Normally, administering these immunomodulatory drugs systemically to a patient can cause lethal toxicity due to activation of immune cells throughout the body. Deep-Primed immune cell therapeutics are designed to activate only the T cells that are going after the tumor, and this is achieved by anchoring the toxic immunomodulatory drugs to the surface of the immune cell to act locally, in the tumor microenvironment.

We call these anchored drugs “backpacks,” which we engineer to either:

  • act on the carrier cell itself (this is known as an autocrine signaling loop), so that the drug is released at the cell surface and binds to the cell’s own receptors; or
  • deliver a drug that activates other immune cells in the microenvironment (this is known as a paracrine signaling loop) to boost the immune response by recruiting other immune cells for a durable, long-lasting anti-tumor efficacy.

Deep-Priming involves two key steps:

  1. Polymerize the immumodulator drugs with copies of themselves to form the backpack that is made out of the drug, connected with a reversible cross-linker
  2. Chemically link the backpack to the carrier T cell, anchoring it to proteins on the T cell surface.

We design the anchor and cross-linkers to respond to the biology of the cell when it finds the tumor, to ensure local release in the tumor microenvironment. Activation of the T cell at the tumor site triggers upregulation of an enzyme on the cell surface, and this chemical reaction dissolves the backpack cross-linkers, releasing the protein so that it can bind to the cell-surface receptors. This process supercharges the immune cell to attack the tumor. In this way, the T cell releases the drug when it recognizes its cancer target.

Deep-Primed T cells retain all the natural functions of natural T cells in vivo, including:

  • trafficking to tissues
  • recognizing tumors
  • destroying tumor cells
Deep-Primed T Cells on the move:
This video shows Deep-Primed T cells migrating through a collagen matrix in cell culture. The blue flashlights visible on the tail of each cell are clustered immunomodulatory drugs carried by the T cell surface receptors. The backpacks have been moved to the rear of the cell, because that’s where the T cell carries those receptors.
A Deep-Primed T cell recognizes and infiltrates its target:
When the Deep-Primed T cell encounters a tumor cell (green), the backpack on its cell surface (blue) starts moving into the interface. The blue speckles show the early stages of the T cell moving the cluster of backpacked immunomodulators into the interface with the tumor cell, where the drug cross-linkers can dissolve and release the drug in a controlled and measured process.
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