Grant: CIHR Fellowship

The immune system is the part of the body that fights infection. Recently, new treatments that use parts of the immune system to fight cancer have been made. One example is chimeric antigen receptor T-cells (CART). With CART, immune cells from a patient are collected. The cells are modified in a laboratory to fight cancer cells. The modified cells are then given back to the patient. CART is very effective at curing some cancers. The most common cancer in children is called acute lymphoblastic leukemia (ALL). ALL has two types: B-cell (B-ALL) and T-cell (T-ALL). CART works well in B-ALL. CART has not yet been used for T-ALL. Children with T-ALL who relapse are very hard to cure. CART could help them. We have tested a CART that targets something on the outside of T-ALL cells called CD38. We call this CART38. CD38 is found at high levels on T-ALL cancer cells but not usually on healthy cells. I have tested CART38 in mice with T-ALL and found it works very well. We will test CART38 in children with T-ALL who received chemotherapy that did not work for them. We will see if CART38 works and if it causes side effects. In some patients, other CART make the immune system overactive. This is called cytokine release syndrome (CRS). Different CART may cause different types of CRS. If we understand CRS after CART38, we can treat it. Understanding CRS is important to make sure that we can use CART38 in children with T-ALL safely. We hope that CART38 will work and cure children with T-ALL. We know with other CART that not all children are cured. We want to make CART38 work even better. In the lab, I will study why T-ALL cells have CD38. I will also study how CART38 kills T-ALL cells. I will look for other medicines that that we can give with CART38 to make the CART38 better at killing T-ALL cells. I hope these studies will lead to better cures for children with T-ALL.