AML (acute lymphoblastic leukemia) is a second major of leukemia cancer. The traditional and well know CAR-T target-CD19 is a specific target of ALL (acute lymphoblastic leukemia)，while it’s quite challenge to find out a specific target for AML. Several years ago, Carl June team developed a promising therapy approach for ALL by using CD19-CAR-T. To cure AML using CAR-T technic, scientists have been searching a long time for its specific targets. Finally, one target-CD33 is recognized as a major target of AML, while the CAR-T based on CD33 didn’t give out a significant therapeutic effects. The major reason is that CD33 is not a specific target for AML cancer T cells. It also express on the normal and healthy cells. When CAR-T-CD33 defense AML cancer cells, the healthy cells are also destroyed. One approach considered is to shorter the staying time of CAR-T in human body, while it’s totally opposite the advantages of CAR-T technology.
To resolve this issue, Saar Gill group and Cynthia E Dunbar group developed a new approach to cure AML by using combined CAR-T with CRISPR technic. They used CRISPR-Cas9 to remove CD33 from health blood forming stem cells, which will lead to that CD33 becomes a specific target of AML cancer cell. Surprisingly, they found that the blood forming stem cells without CD33 can still function same as the regular wild type cells. In that case, CD33-ko stem cells are injected into patient firstly to expand and passage, CAR-T-CD33 then is introduced into body to specific target cancer cells.
By using this combined technology, we could develop artificial specific cancer targets to maximum the potency of CAR-T technology. It would be the next generation of CAR-T therapy. Not only enhance its potency, but also resolve its side-effects issue. It’s a major progress for CAR-T field. Hopefully we could see some promising clinical results soon.
