Technology
Solid tumors represent approximately 90% of all cancers. To date, T-cell therapy such as CAR-T has demonstrated limited success treating solid tumors. We believe two of the barriers limiting the potential of T-cell therapy are the lack of tumor-specific targets and poor tumor infiltration.
We believe we can overcome these barriers by using our proprietary E-ALPHA and ARTEMIS platforms. We have developed E-ALPHA into one of the world’s largest human-derived antibody phage libraries to generate target-specific antibodies, including T cell receptor (TCR)-mimic antibodies against intracellular targets. In addition, we have developed our ARTEMIS Cell Receptor Platform to incorporate the activation pathways of a TCR with proprietary technology to infiltrate solid tumors.
Our proprietary and innovative technology platforms are transforming how cancer is treated.
Click on one of the platform icons below to learn more:
E-ALPHA® Phage Display Platform
Our proprietary E-ALPHA (Eureka Adaptive Library Panning for Human Antibodies) Phage Display Platform is our drug candidate discovery powerhouse, consisting of one of the world’s largest human-derived antibody phage libraries (over 100 billion unique antibody clones) and a robust workflow designed to generate highly specific antibodies against cancer-specific targets:
Targeting the Extracellular Moieties of Cell Surface Proteins
Similar to the receptors on classical Chimeric Antigen Receptor T cells (CAR-T), antibodies derived from the E-ALPHA Phage Display Platform are capable of targeting the extracellular moieties of cell surface proteins that are over-expressed in cancer cells.
Unique Ability to Develop T-Cell Receptor (TCR)-mimic (TCRm) Antibodies Against Intracellular Targets for the Treatment of Solid Tumors
The majority of solid tumor-specific targets are expressed “inside” the cell and were considered “undruggable” using conventional therapies. However, these intracellular targets, like all proteins, are broken down into fragments called peptides. These peptides are displayed on the cell surface by “presenting” molecules, known as major histocompatibility complexes (MHCs). To access these peptide-MHC complexes, Eureka and Memorial Sloan Kettering Cancer Center pioneered the development of TCRm antibodies. Eureka has since developed this technology into a panning system optimized for identifying highly-specific antibodies against intracellular targets, known as the E-ALPHA Phage Display Platform. By incorporating the target binding domain of these TCRm antibodies into the ARTEMIS Cell Receptor Platform, we can generate powerful T-cell therapies capable of accessing solid tumors specifically.
The Mark and Kill Approach
The “Mark and Kill” approach offers a potential treatment solution to cancers where there are no inherently abundant solid-tumor specific targets available. In collaboration with Imugene, using technology such as oncolytic viruses we can force the tumor to express a particular target, then leverage the E-ALPHA Phage Display Platform to produce an antibody specific for that target.
ARTEMIS® Cell Receptor Platform
The ARTEMIS® (Antibody Redirected T Cells with Endogenous Modular Immune Signaling) Cell Receptor Platform is our novel, proprietary technology platform designed to utilize the natural biology of T cells to fight cancer.
KEY COMPONENTS
The Antibody-T-Cell Receptor (AbTCR) is the core component of the platform, featuring:
- A target-binding domain derived from an antibody Fab fragment panned from Eureka’s E-ALPHA Phage Display Platform.
- An effector domain derived from portions of a human gamma/delta (γδ) T-cell receptor (TCR).
The Co-Stimulatory Molecule is an additional key component of the platform featuring:
- A target-binding domain derived from a single-chain variable fragment (scFv) panned from Eureka’s E-ALPHA Phage Display Platform.
- A co-stimulatory domain derived from portions of a human co-stimulatory receptor.
The AbTCR and Co-Stimulatory Molecule components together create the ARTEMIS® Cell Receptor Platform.
How Do ARTEMIS T Cells Fight Cancer?
During the manufacturing process, T cells are engineered to express ARTEMIS cell receptors (i.e., the AbTCR and co-stimulatory molecule) on their cell surfaces. The resulting “ARTEMIS T cells” are expanded and then cryopreserved for delivery to patients.
Once infused, ARTEMIS T cells engage target-positive cancer cells. The AbTCR expressed on the ARTEMIS T cell naturally associates, via its effector domain (gamma/delta TCR chains), with the endogenous CD3 complex. When the AbTCR binds to its target expressed on the cancer cell, AbTCR/CD3 complex-mediated signal transduction within the T cell is initiated. This signal transduction process ultimately leads to the activation of the ARTEMIS T cell.
A second “enhancement” signal is generated when the co-stimulatory molecule expressed on the ARTEMIS T cell binds to its target expressed on the cancer cell. The main function of the co-stimulatory molecule is to “boost” AbTCR signaling, resulting in increased expansion and survival of ARTEMIS T cells inside the body. The co-stimulatory molecule has also been optimized to provide ARTEMIS T cells with an enhanced ability to infiltrate solid tumors. In summary, ARTEMIS T cells seek out target-positive cancer cells, bind to these cells, and destroy them.
Key features and Advantages of the E-ALPHA and ARTEMIS Technologies:
| Key Feature | Advantage |
|---|---|
| Antibody-based target recognition | Achieve high specificity and binding affinity to intended cancer target. |
| AbTCR includes portions of a human TCR | The AbTCR associates with the endogenous CD3 complex enabling the AbTCR to use the same activation and regulatory signaling pathways employed by natural TCRs. This feature may lead to improved safety in patients. |
| Co-stimulation provided as a separate molecule | The AbTCR construct does not include an intracellular signaling domain covalently-linked to a co-stimulatory domain, and thus has the potential to eliminate T-cell hyperactivation and consequently, lower the risk of cytokine release syndrome (CRS) and neurotoxicity commonly observed with CAR-T therapy. |
| Co-stimulation molecule designed to enhance the ability of ARTEMIS T cells to infiltrate solid tumors | In developing the co-stimulatory molecule, we selected a co-stimulatory domain that enhanced the ability of ARTEMIS T cells to infiltrate solid tumors in animal models, potentially leading to improved efficacy in patients. |
