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Bispecific Antibodies Enable Targeted Treatment for Leukemias

A new treatment approach for leukemia that uses antibodies to deliver chemotherapeutic drugs specifically to cancer cells while sparing normal tissues is reported in Science Translational Medicine this week. For many aggressive cancers, intense chemotherapy regimens are the only treatment options, but these carry risks of neurotoxicity, organ dysfunction, and deadly cytokine release syndrome. Aiming to address these issues, a team led by scientists from the Lowy Cancer Research Center at the University of New South Wales in Australia combined liposomal nanocarriers, which can be used to encapsulate chemotherapeutics to improve biodistribution and drug tolerability, with interchangeable bispecific antibodies that bind to both the nanoparticle surface and different receptors on cancer cells. Focusing on high-risk childhood leukemias, they show that the approach can improve the targeting and cytotoxic activity of a clinically approved liposomal formulation of the chemotherapeutic doxorubicin both in leukemia cell lines and patient samples while reducing toxicity. Complexing the doxorubicin formulation to bispecific antibodies also enhanced the drug's in vivo therapeutic activity in patient-derived xenograft models. "This treatment approach represents an alternative therapeutic option for children with high-risk leukemia that is applicable to diverse forms of the disease, exhibits low toxicity, and does not rely on complex methodologies to succeed," the researchers write. It also holds potential for other blood cancers, they note.