CAR-Treg

CAR-Treg

ENGINEERING THE IMMUNE SYSTEM TO COMBAT NEURODEGENERATION

Excessive neuroinflammation amplifies neurodegenerative diseases, including Alzheimer’s disease, Amyotrophic Lateral Sclerosis (ALS), Parkinson’s disease, Progressive Supranuclear Palsy, Frontotemporal Dementia (FTD), and Multiple Sclerosis (MS).

Regulatory T cells (Tregs) are a T lymphocyte subpopulation that maintain homeostasis in the immune system, mediate immune tolerance, and suppress activities of other immune cells. As such, Tregs are an ideal cell for immune-engineering methods to combat neurodegeneration.

The immunomodulatory effects of Tregs have been widely investigated in central nervous system (CNS) disorders, and have been shown to confer protection in models of Alzheimer’s disease, ALS, stroke, Parkinson’s disease, and MS and related pathologies. Further, a Phase 1 clinical trial demonstrated that autologous (the patient’s own) Treg infusions reduce disease progression in ALS patients, however, autologous Tregs target the CNS inefficiently and also require frequent and large infusions to induce a therapeutic effect. Further, patients with many of these conditions have Treg abnormalities, reducing the efficacy of an autologous approach.

AZTherapies is pioneering an allogeneic (non-self) CAR-Treg platform that aims to:

  • harness the anti-inflammatory and immune-dampening functions of Tregs in the CNS,
  • engineer Tregs with a chimeric antigen receptors (CAR) to target the CNS and potentially improve efficacy and safety of the cell therapy while reducing required infusion volume/frequency, and
  • leverage proprietary technology to generate allogeneic, off-the-shelf cell therapies to reduce the patient burden and production hurdles associated with current therapies.

We are currently validating our cell therapy platform in human in vitro assays and in vivo models of neurodegenerative diseases, with initial proof-of-concept expected to read out in mid-2020. (See Pipeline for more on the clinical development of our CAR-Treg platform)

Image from paper by Hu, X Mechanisms underlying regulatory T cell- mediated neuroprotection or regeneration

MECHANISMS UNDERLYING REGULATORY T CELL – MEDIATED NEUROPROTECTION OR REGENERATION

Source: Hu, X et al., 2018, Nature Reviews | Neurology, Macmillan Publishers Limited

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