Treatment of acute myeloid leukemia with CAR-T cells

Genetic Inactivation of CD33 in Hematopoietic Stem Cells to Enable CAR T Cell Immunotherapy for Acute

Myeloid Leukemia

May 31, published in the Cell magazine entitled "Genetic Inactivation of CD33 in Hematopoietic Stem Cells to Enable CAR T Cell Immunotherapy for Acute Myeloid Leukemia," Dr. Saar Gill of the University of Pennsylvania School of Medicine and National Health The team led by Dr. Cynthia E. Dunbar of the Institute pioneered a new approach to treating acute myeloid leukemia (AML) with CAR-T cells.

AML is the second most common leukemia type and many patients will receive bone marrow transplants. A few years ago, in order to treat acute lymphoblastic leukemia (ALL), Professor Carl H. June and others developed a CAR-T therapy targeting CD19  and obtained FDA approval last  year. However,  CD19  is not an effective target for AML because such cancer cells do not express the molecule.  Therefore, scientists are always looking for other potential targets for AML.

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In the end, a protein called CD33 gave them hope. Unfortunately, previous attempts have found that CAR-T cells that target CD33 also damage healthy cells because the protein is also expressed in  healthy cells. Although damage to healthy cells can be prevented by shortening the duration of CAR-T cells,  this method is contrary to the greatest advantage of CAR-T therapy - it can persist in  patients  for  many years to prevent the recurrence of the disease.

So, how can let CAR-T cells that target CD33 both attack cancer cells and avoid damaging healthy cells?  Scientists  thought  of the gene editing tool CRISPR/Cas9.

Image Source: Cell

Specifically, the new method invented by Dr. Gill and others uses this "magic scissors" to remove CD33 in healthy blood-forming stem cells,  making the cancer cells a "CD33  hunter cell." That is,  the  target of CD33-targeted CAR-T cells is the only one  that can attack.  Very importantly, they were  pleasantly  surprised  to find that healthy stem cells lacking CD33 also function properly.  As a result,  CAR-T therapies  targeting CD33 can exert anti-cancer effects without damaging healthy cells.

Dr. Gill said: "In addition to EGFRvIII in brain cancer, none of the existing CAR-T therapies  are directed against cancer-specific antigens (that is, the  cancer cell antigens normally  targeted  by CAR-T cells are also found in  healthy  cells.)  (Expressed),  but using the new method  proposed  in this study, we can artificially  “create” cancer-specific antigens to release  the  greatest anti-cancer strength of  CAR-T cells.  We can think of  this approach as version 2.0  ( The next generation  of bone marrow  transplantation not only gave CAR-T cells superior anti-leukemia but  also solved  major  toxicity  problems."

Dr. Dunbar believes that this study is an important development in the effectiveness and safety of CAR-T therapy in the treatment of leukemia. Currently, they have  demonstrated that the  method is  effective in mouse  and monkey models, and also confirmed the effect of this method on  human  cells  in the laboratory environment. Next, the team will conduct human trials at the University  of  Pennsylvania.

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