CRISPR to Distinguish Cancer Cells from Normal Cells

CAR-T therapy made history as the first living drugs for cancer. Particularly effective in hematological cancers (originating in the blood and bone marrow), CAR-T can cause some damage to healthy cells. Research into reducing the toxicity (side effects) of CAR-T therapy has recently increased. In June 2018, Cell published a study in which CRISPR genetic engineering technology was used to make CAR-T therapy more specific (selective) and safer in AML.

Acute myeloid leukemia (AML) is the second most common type of leukemia. Most patients undergo stem cell / bone marrow transplantation . Recently, FDA-approved CAR-T cell therapies target cancer cells in which the CD19 protein is active. These treatments are used for ALL and Hodgkin lymphoma. They are not effective in AML because the CD19 protein is not active in AML cells. Researchers therefore focused on the CD33 protein, which is active in AML. CD33 is also active in healthy cells. A drug targeting CD33 would therefore also seriously damage healthy cells. For this reason, researchers used the crispr/cas9 technique to inactivate the CD33 protein in healthy cells. This would allow AML cells to be targeted without harming healthy cells.

What Does This Study Tell Us?

• A method that could increase the effectiveness of CAR-T cell therapies, described as the first living drugs for cancer, was developed using CRISPR.
• This will allow CAR-T cell therapy to be specific to the cancer antigen. Safer and more specific (individualized, selective) CAR-T would cause less damage to healthy bone marrow cells.
• The approach was found effective in monkey and mouse models. Its effects were also demonstrated in human cells in the laboratory. Following confirmation in humans through clinical trials , it will become available for clinical use.
• We can think of this method as stem cell transplantation 2.0 . This has opened the door to treatments with fewer side effects.