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Jul 30, 2023

New treatment for aggressive child cancers developed in Australia

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Scientists at the Children's Cancer Institute (CCI) and UNSW Sydney have found a way to get treatment drugs to act selectively on cancer cells in the body leading to safer and more effective treatment options for children with aggressive blood cancers.

This is according to a press release published by the institution on Thursday.

"Finding a way to make treatment drugs act more selectively on cancer cells is the key to improving treatment success while reducing toxicity in children treated for high-risk leukaemia," said lead researcher Professor Maria Kavallaris AM, from UNSW Medicine & Health and CCI.

"By specifically targeting leukaemia cells, we can make treatment more effective, as well as much safer to use in children."

The researchers involved in the work are praising the new approach's flexibility.

"What is particularly useful about this new approach is its flexibility," said the study's first author, Dr Ernest Moles, from UNSW Medicine & Health and CCI.

"We can use this system to target any leukaemia, including the high-risk subtypes that are killing Australian children every year. Rather than having to design a completely new therapeutic each time, all we need do is change the antibody bridge, and we can target the same drug to any child's blood cancer.

"What's more, this approach could allow us to counter drug resistance in an individual patient. If the cancer cells in a child try to evade chemotherapy by altering their cell surface, we can modify the targeted drug delivery system so it is able to recognise that altered cancer cell. There will be no easy escape."

Best of all, the new treatment was found to work well not only in leukemia cells grown in the laboratory, but also in living models of disease, leading the scientists to have very high hopes for the approach.

"In the future, it may be that each child diagnosed with leukaemia can have their treatment targeted to their specific subtype, based on the analysis of a blood sample," Kavallaris said in the statement.

"We believe the controlled targeting of nanotherapeutics represents a real milestone in the treatment of childhood cancers, and we’re very optimistic about where this could lead to."

The study was published in the journal Science Translational Medicine.

Study abstract:

High-risk childhood leukemia has a poor prognosis because of treatment failure and toxic side effects of therapy. Drug encapsulation into liposomal nanocarriers has shown clinical success at improving biodistribution and tolerability of chemotherapy. However, enhancements in drug efficacy have been limited because of a lack of selectivity of the liposomal formulations for the cancer cells. Here, we report on the generation of bispecific antibodies (BsAbs) with dual binding to a leukemic cell receptor, such as CD19, CD20, CD22, or CD38, and methoxy polyethylene glycol (PEG) for the targeted delivery of PEGylated liposomal drugs to leukemia cells. This liposome targeting system follows a "mix-and-match" principle where BsAbs were selected on the specific receptors expressed on leukemia cells. BsAbs improved the targeting and cytotoxic activity of a clinically approved and low-toxic PEGylated liposomal formulation of doxorubicin (Caelyx) toward leukemia cell lines and patient-derived samples that are immunophenotypically heterogeneous and representative of high-risk subtypes of childhood leukemia. BsAb-assisted improvements in leukemia cell targeting and cytotoxic potency of Caelyx correlated with receptor expression and were minimally detrimental in vitro and in vivo toward expansion and functionality of normal peripheral blood mononuclear cells and hematopoietic progenitors. Targeted delivery of Caelyx using BsAbs further enhanced leukemia suppression while reducing drug accumulation in the heart and kidneys and extended overall survival in patient-derived xenograft models of high-risk childhood leukemia. Our methodology using BsAbs therefore represents an attractive targeting platform to potentiate the therapeutic efficacy and safety of liposomal drugs for improved treatment of high-risk leukemia.