For the first time in Canada, blood stem cells have been genetically modified using CRISPR-Cas9 technology, as part of an international clinical trial for leukemia and other aggressive blood cancers.
Published in Nature Medicine, the trial was led by Université de Montréal medical professor Léa Bernard at the UdeM-affiliated Hôpital Maisonneuve-Rosemont (HMR)'s Institut universitaire d'hématologie-oncologie et de thérapie cellulaire (IHOT).
In many cases of acute leukemia, stem cell transplantation is the only hope for a cure; however, this is not guaranteed, as the rate of post-transplant relapse remains high.
New immunotherapies show promise, but they present a major problem: they attack not only cancer cells, but also normal blood cells, leading to significant side effects.
To work around this problem, Bernard's research team used a cutting-edge technology called CRISPR-Cas9 — a kind of "molecular scissors" that allows DNA to be modified with great precision.
The researchers first removed the CD33 molecule from cells collected from donors, then infused them into patients. CD33 is a molecule found on both the patient's cancer cells and the donor's healthy blood cells.
Anti-CD33 drugs are effective against cancer, but they also destroy healthy cells, causing significant side effects. By removing the CD33 gene from the donor's stem cells using CRISPR-Cas9 before transplantation, those cells are rendered invisible to the drug.
The result: after transplantation, the patient's new blood cells derived from these modified stem cells no longer carry the CD33 marker.
The treatment can then exclusively target and destroy residual leukemic cells, without affecting the patient's new blood system — thereby reducing the risk of relapse, Bernard's research revealed.
