Estrella is extending the curative power of T-cell therapies to more cancer indications by combining CD19-Redirected ARTEMIS T Cells with cancer-labeling technology.
The Challenge
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The initial class of chimeric antigen receptor (CAR) T-cell therapies have shown remarkable efficacy in certain CD19-positive blood cancers such as lymphomas and leukemias. However, its life-threatening side effects, such as Cytokine Release Syndrome (CRS) and neurotoxicity have limited currently approved CAR-T therapies to specialized centers and later lines of treatment.
The Limitations of CAR-T
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Solid tumors represent approximately 90% of all cancers. To date, T-cell therapies such as CAR T-cell therapy have demonstrated little success in treating solid tumors. We believe that two major barriers to fully unleashing the power of T-cell therapy are the lack of tumor-specific targets and poor tumor infiltration.
Beyond Blood Cancers
Our Solution
A Next-Generation CD19 Immunotherapy
Inspired by the natural biology of T cells, we have designed our proprietary CD19-Redirected ARTEMIS® T Cell to significantly mitigate the CRS and neurotoxicity risks while aiming to deliver persistent efficacious cancer treatment.
Unlike a traditional CAR-T cell, the unique structure of a CD19-Redirected ARTEMIS T Cell allows it to form a multimeric T-cell signaling complex with the endogenous CD3 chains of the T cell upon engagement with cancer targets, utilizing the natural activation and regulatory pathways of the T-cell receptor (TCR) to control the production of cytokines.
In a proof-of-concept (POC) clinical study, 12 relapsed/refractory B-cell lymphoma patients were treated with our CD19-Redirected ARTEMIS T Cells. 83% of evaluable patients achieved an overall response rate (ORR), including 6 patients with a complete response (CR). No patients experienced severe (grade >=3) CRS.
CD19-Redirected ARTEMIS T Cells
The key units of our novel, proprietary CD19-Redirected ARTEMIS (Antibody Redirected T Cells with Endogenous Modular Immune Signaling) T Cells comprise of an antibody-T-cell-receptor (AbTCR) and a co-stimulatory molecule:
The Antibody-T-Cell Receptor (AbTCR) serves as the core component featuring:
• A target-binding domain derived from an antibody fragment antigen-binding (Fab) region
• An effector domain derived from portions of a human gamma/delta (γδ) TCR
The Co-Stimulatory Molecule is an additional key component featuring:
• A target-binding domain derived from a single-chain variable fragment (scFv)
• A co-stimulatory domain derived from portions of a human co-stimulatory receptor
Both the AbTCR and the co-stimulatory molecule bind to the CD19 antigen, a well-validated target commonly overexpressed on blood cancer cells.
The Mark-and-Kill Approach
To address the issue of the lack of solid tumor-specific targets, we use an oncolytic virus to force solid tumor cells to express the CD19 protein on the cell surface. The CD19-Redirected ARTEMIS T Cells can then pursue and kill the CD19-labeled solid tumors, offering a potential treatment solution to cancers where there are no inherently abundant solid tumor-specific targets available.