HSCs are genetically engineered to remove target protein
Pioneering a New Approach
We make healthy cells invisible to targeted therapies
Targeted therapies attack cells that express particular proteins on their surface. Unfortunately, both diseased and healthy cells often express the same proteins, leading to collateral damage of healthy cells.
To solve this challenge, we engineer hematopoietic stem cells (HSCs) to lack a target protein that is biologically redundant (meaning it does no harm when it is removed). We then transplant these eHSCs into the patient.
These eHSCs lead to generations of new healthy blood cells and the eHSCs can continue functioning normally because they are effectively hidden from the therapies that target the relevant protein. In contrast, diseased cells retain the target protein and are vulnerable to attack. This process potentially broadens the therapeutic window and improves the utility of complementary targeted therapies.
The patient is prepared to receive a hematopoietic stem cell transplant and HSCs are collected from a matched, healthy donor.
eHSCs are transplanted into the patient
eHSCs create the full range of healthy blood cells
The patient may then receive a therapy that now only attacks the diseased cells that still have the target protein.
Targeted therapy NOW attacks only cancer cells
The power of the platform
By rendering healthy cells “invisible” to targeted therapies, we aim to significantly broaden the therapeutic window and improve the utility of these therapies, with the goal of increasing clinical benefit to patients. Potential advantages include:
Enabling earlier therapy
Allowing different dosing strategies
This platform is designed to usher in a new generation of targeted therapies to dramatically enhance treatment of diseases such as cancer
The platform is highly flexible, with enormous potential. By design, our approach encompasses the editing of a single gene or several genes, enabling more effective treatment of multiple kinds of cancer with existing targeted therapies.
We’re also identifying a new category of amenable targets — biologically redundant proteins — that we can remove with gene editing, thereby making these targets cancer-specific and enabling the development of novel therapies targeting those proteins.
• Gene-edited stem cells enable CD-33 directed immune therapy for myeloid malignancies. Borot F, Wang H, Ma Y, Jafarov T, Raza A, Ali AM, and Mukherjee S. PNAS. 2019 Mar
• Engineering resistance to CD-33 targeted immunotherapy in normal hematopoiesis by CRISPR/Cas9-deletion of CD33 exon 2. Humbert O, Laszlo GS, Sichel S, Ironside C, Haworth KG, Bates OM, Beddoe ME, Carrillo PR, Kiem HP, Walter RB. Leukemia. 2019 Mar; 33(3):762-808