Scientists from the University of Manchester found that the 5T4 protein, found on the surface of cells, promotes resistance to chemotherapy in children with leukemia. Their findings show that the effect on the protein using an antibody-drug (drug-loaded antibodies) can improve treatment outcomes.
Over the years, the survival rate of children with acute lymphoblastic leukemiahas improved. Now, about nine out of ten young patients can expect to recover, but used treatments - usually an intensive course of chemotherapy - can leave children with lifelong side effects (secondary infertility and even cancer). There is also a likelihood of recurrence of the disease, when, after the first cycle of intensive treatment are high levels of initiating leukemia cell. In this case, the cancer cure even harder.
In the study, researchers analyzed tissue samples from children with low and high risk of recurrence, calculated by the number of leukemia cells that are left after the first course of chemotherapy. They found a large number of leukemia cells to 5T4 in patients with high risk of recurrence. This marker was not found in samples taken from children who passed the initial treatment.
The researchers found that the protein helps stem 5T4 leukemia cells migrate from the blood vessels in the bone marrow during therapy. This complicates thetreatment of cancer .
The scientists used the antibody - drug A1mcMMAF, which acts on the molecule 5T4, in mouse models, and achieved good results of the treatment. And combining it with dexamethasone, a standard component of induction therapy, they were able to increase the survival of rodents.
Results of the study show that leukemia-initiating cells that have 5T4, easier to penetrate into the areas of the body that protect them from chemotherapy, causing resistance and relapse of drug. But scientists can selectively attack resistant to the treatment of leukemia cells and reduce the side effects of using targeting 5T4.
The study was published in «Bloodwise» magazine.