Human Embryonic Stem Cell-Derived Natural Killer Cells for Cancer Treatment

Translational Candidate

Human embryonic stem cell (hESC)-derived natural killer (NK) cells to target relapsed/refractory Acute Myelogenous Leukemia (AML)

Area of Impact

hESC-derived NK cells provide a novel and potent approach to treat relapsed or refractory AML that is resistant to current chemotherapy options.

Mechanism of Action

hESC-derived NK cells provide a standardized, homogeneous, off-the-shelf cellular immunotherapy product that will be used as an allogeneic adoptive transfer treatment for patients with AML who have either never achieved remission with standard induction therapy, or who relapse after previous chemotherapy. hESC-derived NK cells kill tumor cells by several mechanisms: direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity, induction of apoptosis and production of cytokines.

Unmet Medical Need

Over 10,000 in the US die each year from AML, with 5 year survival <30%. Allogeneic NK cells are known to destroy AML cells in patients who have failed chemotherapy. hESC-derived NK cells will provide the first standardized, "off-the-shelf" cellular immunotherapy to treat this deadly disease.

Project Objective

The objective is to have an FDA Pre-IND meeting

Major Proposed Activities

• We will use the GMP hESC line ESI-017 to produce a Master Cell Bank and Working Cell Bank of NK cells using defined clinical-scale cell methods.
• We will demonstrate ESI-017 hESC-derived NK cells kill AML tumor cells 1) in vitro, and 2) in vivo using NSG mouse xenograft models.
• We will assess safety of ESI-017 hESC-derived NK cells using NSG mouse model and in vitro assays to test tumorigenicity and lack of off-target killing