Good news! Cancer is history (soon)!
"The genetically modified immune cells known as CAR-T cells have cured thousands of people with blood cancers, but so far the treatments only work against a few types of the disease. Today in Science Translational Medicine (STM), a research team describes a provocative CAR-T strategy to tackle most blood cancers. Working in mice, the scientists sicced the immune cells on a protein common to nearly all cancerous blood cells. Because that protein is also found on normal blood-forming stem cells, the team also replaced those vital cells with ones genetically tweaked to be invisible to the cancer fighters, protecting them from the onslaught. ...
A team ... came up with a clever way to avert these attacks. Their first step entailed creating CAR-T cells that pounce on cells with CD45. To keep those cells from attacking each other, the team used the CRISPR genome editor to make a small change in sequence of the T cell gene encoding CD45, altering the protein just enough to conceal it from the CAR-T receptor. To protect the normal blood cells that carry CD45, the group made the same change in a line of blood stem cells. ..."
From the abstract:
"In the absence of cell-surface cancer-specific antigens, immunotherapies such as chimeric antigen receptor (CAR) T cells, monoclonal antibodies, or bispecific T cell engagers typically target lineage antigens. Currently, such immunotherapies are individually designed and tested for each disease. This approach is inefficient and limited to a few lineage antigens for which the on-target/off-tumor toxicities are clinically tolerated. Here, we sought to develop a universal CAR T cell therapy for blood cancers directed against the pan-leukocyte marker CD45. To protect healthy hematopoietic cells, including CAR T cells, from CD45-directed on-target/off-tumor toxicity while preserving the essential functions of CD45, we mapped the epitope on CD45 that is targeted by the CAR and used CRISPR adenine base-editing to install a function-preserving mutation sufficient to evade CAR T cell recognition. Epitope edited CD45 CAR T cell were fratricide-resistant and effective against patient-derived acute myeloid leukemia, B cell lymphoma, and acute T cell leukemia. Epitope edited hematopoietic stem cells (HSCs) were protected from CAR T cells and, unlike CD45 knockout cells, could engraft, persist, and differentiate in vivo. Ex vivo epitope editing in HSCs and T cells enables the safe and effective use of CD45-directed CAR-T cells and bispecific T cell engagers for the universal treatment of hematologic malignancies and might be exploited for other diseases requiring intensive hematopoietic ablation."
No comments:
Post a Comment