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Pipelines

Stem Medicare is developing EV-based new drugs for various diseases

as well as regenerative medicines based on the world's only non-immunogenic,

immune-tolerized extracellular vesicle technology.

Pipelines

Anti-Cancer

Tumor Microenvironment (TME) for immune escape

High level of
lactate and low pH
by Warburg effect
Our immune system performs a normal immune surveillance role by immediately recognizing and eliminating cancer cells or mutant cells generated by various causes. To evade this immune response, cancer cells change their metabolism to form a tumor microenvironment characterized by high lactate concentrations and low pH.
Low pH in Tumor Microenvironment (TME)
Low pH
Tumor Microenvironment
  • Cytotoxic & helper T cells
    • IL-2, IFN-γ, TNF-α secretion
    • Perform & granzyme
      production and cytotoxic activity
    • Proliferation in response to activation
    • Metabolism, chemotaxis,
      and specific CTL responses
  • NK cells
    • Inhibition of NFAT upregulation NKp46 (major Activating receptor) expression
    • Cytotoxic activity
    • Degranulation
    • Metabolic activity
    • Proliferation
  • Antibodies
    • Degradation
    • Oxidation
    • Fc aggregation
    • Antigen binding activity
High level of
lactate in Tumor
Microenvironment
High Lactate
Tumor Microenvironment
  • T cells
    • Lactic acidosis (low pH)
    • Induction of apoptosis by reduced
      level of cytoplasmic NAD+
    • Inhibition of p38 and JNK//c-JUN
      pathway important for IFN-γ production
    • Inhibition of lactate efflux
    • Inhibition of mTOR pathway
  • NK cells
    • Lactic acidosis (low pH)
    • Inhibition of NFAT
      (nuclear factor of activated T cells)
      important for IFN-γ production
    • Inhibition of mTOR pathway
  • NKT cells
    • Lactic acidosis (low pH)
    • Inhibition of mTOR pathway
    • Inhibition of PPARγ/SREBP1 pathway
      important for IFN-γ and IL-4 production
  • Monocytes and Dendritic cells
    • Lactic acidosis (low pH)
    • Induction of differentiation into DCs with an immunosuppressive
      phenotype
    • Activation of GPR81 to inhibit MHC-II expression
    • Activation of MCTs-mediated lactate influx leading inhibition of type I
      IFN production
  • Macrophages
    • Lactic acidosis (low pH)
    • Inhibition of M1 functions by reducing the expression of IL-6,
      iNOS, and CCL2
    • Induction of M2 polarization
    • Lactate-mediated stabilization of HIF-1a
    • Activation of ERK/STAT3 pathway and GPR132
    • Lactylation of histones causing epigenetic modifications

Innovative anti-tumor immune-tolerized extracellular vesicles therapeutics (MBTC-AT-EVs)

Reverse Warburg effect to normalize tumor environment
MBTC-AT-EVs

  • Immune-tolerized extracellular vesicle therapeutics for anti-tumor
    (solid tumor more than 90% of adult cancer)

  • MOA : Normalize tumor microenvironment (TME) via reducing Lactate and H+ efflux through
    “REVERSE Warburg Effect” in which lactate convert pyruvate by LDHB and PGC-1a in MBTC-AT-EVs

  • Capable to be used alone or in combination with immuno-oncology including immune checkpoint
    inhibitor and/or immune cell therapy (CAR-T, CAR-NT, and CAR-DC, etc.)