Promising Results Shown For CRISPR
CRISPR has shown promising results in preliminary clinical studies to correct sickle cell disease and treat blindness, transthyretin amyloidosis, and hereditary angioedema. A new study in collaboration with University College London and Great Ormond Street Hospital for Children investigated the potential feasibility of base-edited CD7-targeted chimeric antigen receptor (BE-CAR7) T cells to induce remission in children with relapsed/refractory (r/r) CD7-positive T-cell acute lymphoblastic leukemia (T-ALL), prior to an allo-stem cell transplant (allo-SCT). To circumvent the challenges associated with human leukocyte antigen (HLA) barriers that prevent or severely hinder the use of CAR-T therapies, scientists have developed a CRISPR-based and guided cytidine deamination process that mediates a highly precise C→U→T conversion that directly disrupts gene expression without causing DNA breaks.
The novelty of the study included 4 key milestones. The first is deleting all existing T-cell cell surface markers with no need for HLA matching, making them universal and allowing for the possibility of having ready-made “off-the-shelf” CAR-T therapies. Second, remove CD7 to avoid T-cell fratricide when introduced to a new host. Third, the deletion of CD52, which makes T-cells invisible to some of the potent drugs the patient may receive during therapy. Finally, adding CAR that recognizes CD7 receptors, thus targeting T-cell leukemia. Using this technology, a 13-year-old girl named Alyssa was the first ever reported to receive the BE-CAR7 therapy. Diagnosed in 2021 and after chemotherapy and a bone marrow transplant, before the based-edited treatment, her medical team could not control her cancer. She entered remission within a month after the administration of BE-CAR7 and received a second bone marrow transplant to restore her immune function. Six months post-transplant, her cancer remains undetectable.