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.

Treatment process

The patient is prepared to receive a hematopoietic stem cell transplant and HSCs are collected from a matched, healthy donor.

HSCs are genetically engineered to remove target protein

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:

Reducing toxicity

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.

icon-1

Publications

Decentralized manufacturing: from stem cell transplants to the next generation of cellular immunotherapies. Li M, Kassim S. Cell & Gene Therapy. 2020 June.

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