Hyper-targeting CAR NK cells from induced pluripotent stem cells for novel off-the-shelf anti-tumor therapies

Introduction

The HyperTargIPS-NK project aims to combine novel technologies from three research laboratories and a stem cell company to develop a revolutionary therapeutic modality for patients with devastating refractory malignancies.

Treatment Overview

The treatment we propose is based on allogenic transplantation of induced pluripotent stem (iPS) cell-derived natural killer (NK) cells, genetically modified to a hyperactive state to ensure high potency NK cell targeting and destruction of tumor cells. CAR NK-based cancer treatment is an extremely promising new therapeutic avenue.

Challenges and Solutions

However, the full potential of CAR NK therapies will only be achieved when an off-the-shelf product is rapidly accessible to patients in need. IPS, with its unlimited expansion potential, is the ideal cell source for NK-based products.

Key Challenges

To realize this potential, the following improvements are necessary:

1. Improved efficiencies of NK cell production
2. Suitably activated status
3. Resistance to immune suppression

We have several breakthrough technologies to address these issues:

1. A novel iPS cell differentiation system based on our newly identified metabolic regulators that can be easily scaled to generate billions of functional NK cells.
2. Identified and validated several novel and state-of-the-art CAR, non-CAR, and TRUCK-based regulators of NK activation to elicit the hyper-activated NK cell state and prolong NK survival.
3. Improved NK response to tumors via tumor microenvironment remodeling.

Target Cancers

We will target the NK cells towards three life-threatening cancers for which novel treatment options are urgently needed, as they are considered among the most lethal cancers:

• Pancreatic cancer
• Glioblastoma
• Acute Myeloid leukemia (AML)

GMP Compatibility

Our iPS culture system, NK activation systems, and gene editing systems have already been designed towards GMP compatibility. Taken together, these advances ensure that once this study is successful, our Hyper-Targ-IPS-NK cells are poised for rapid translation towards the clinic with our industrial partner.