An antibody drug conjugate may combat ALL

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An antibody drug conjugate may combat ALL

Postby whbio » May 19 2017 4:16 pm

Acute lymphoblastic leukemia (ALL) is the most common form of cancer among children, although it can be also diagnosed in adults. The five-year survival rate for childhood ALL has been significantly improved over time and is now 90%. Treatment for the disease generally includes intensive chemotherapy, which may come with a long list of side effects, such as anemia, infection, bleeding, hair loss, and even an increased risk of developing a secondary cancer.

Now researchers have found a new way to treat the diseases. The main findings of the study are that the 5T4 oncofoetal glycoprotein on cell surface may be the cause of chemotherapy resistance in ALL, and that targeting 5T4 with an antibody drug conjugate improved outcomes of mice engrafted with 5T4 positive patient derived xenograft cells.

In this work, lead researcher Prof. Peter Stern of the University of Manchester and the team examined samples from children with ALL with low or high risk of relapse. It is well known that leukaemic cells that remain in patients after remission induction therapy is the major cause of relapse. So the number of leukaemic cells remaining can help predict outcome of childhood ALL. Those with larger numbers of leukaemic cells remaining tend to have inferior results.

The investigators found a high proportion of 5T4 positive leukaemia cells in patients with a high risk of relapse but not in children who responded well to initial treatment. Further investigation showed that 5T4 positive leukaemia cells are more clonogenic and preferentially localised to bone marrow, making it more difficult for chemotherapy drugs to kill them.

When the investigators used a 5T4-antibody drug conjugate, called A1mcMMAF, to treat mice engrafted with a 5T4 positive ALL cell line, the survival of the mice were greatly improved. Moreover, A1mcMMAF treatment did not cause toxic effects.

The study "Targeting The 5T4 Oncofoetal Glycoprotein With An Antibody Drug Conjugate (A1mcmmaf) Improves Survival In Patient Derived Xenograft Models Of Acute Lymphoblastic Leukemia" appears in the journal Haematologica. (Cusabio offers antibodies.
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