The Science cdn_helper

Cancer Can't shield itself from the immune system Anymore

  • We’ve found–and patented–a novel way for the immune system to attack cancer by modifying Treg cells
  • Enhancing the immune system’s ability to infiltrate and destroy cancer

SRCs are master regulators of the genome

First discovered in O’Malley lab
300 publications since 1995

Steroid Receptor Activators (SRCs) activate groups of genes to achieve the following physiological outcomes:

SRC-1 regulates gluconeogenesis and appetite

SRC-2 regulates lipid metabolism and storage

SRC-3 regulates growth and immunity and controls gene expression

Regulates 75% of genes in cancer cells

  • Treg act as negative regulators to keep the immune system in check
  • SRC-3 controls hundreds of genes in Treg that suppress T-effector cells that kill cancers

Works in the nucleus

Not on the cell surface like other therapies

CoRegen works in the nucleus, allowing desired outcomes without typical side effects. Our genetically engineered Treg cells:

Are phenotypically altered without fully inhibiting their immune checkpoint function

No longer blocks immune effector cells in the tumor microenvironment

  1. Infused engineered SRC-3 KO Treg infiltrates into tumors
  2. Cancer-killing immune cells are now able to function within tumors
  3. The combined actions of SRC-3 KO Treg and immune effector cells eliminate tumors

Benefits:

  • T memory cell population is increased in animals treated with engineered SRC-3 KO Treg cells
  • Smaller number of engineered SRC-3 KO Treg dominate over existing normal Treg cells within tumor tissue
  • SRC-3 KO Treg attract CD8+, CD4+ and NK tumor killing effector cells into tumors

Why it works

Employs a unique mechanism of action

1. CoRegen targets SRC-3

Targeting the SRC-3 in Tregs in proteins enables broad changes in protein expression that impact the immune system’s ability to engage and attack cancer cells

2. Blocks Treg activity

…by replacing normal Treg cells within the tumor microenvironment, thus killing tumors without the need for lymphodepletion.

3. Engineered Treg cells:

  • Functionally dominate normal Treg within tumors but not in the rest of the body, supporting normal Treg functionality outside of the tumor.
  • Express much larger amounts (~20x) of a key cytokine receptor (IL2RA) that aggressively recruits engineered SRC-3 KO Treg into tumors.
  • Produce large amounts of IFNγ (10x) which causes a large influx of anti-tumor immune effector cells (CD8/CD4 and NK) into tumors.
  • Produce significantly more perforin (9x) and granzymes (6x) that drive the destruction of cancer cells in the tumor.
  • Increased T memory cell population after engineered SRC-3 KO Treg treatment.

4. Shown to be safe and nontoxic

Not known to cause a cytokine storm or apparent toxicity in animal models.