Selective targeting of cancer cells in new treatment approach
Australian scientists have developed a new method to solve a decades-old clinical problem: getting treatment drugs to act selectively on cancer cells in the body.
Published in the journal Science Translational Medicine, the team’s research paves the way to safer and more effective treatment options for children with aggressive blood cancers, and potentially other types of cancer as well.
Chemotherapy is the mainstay of treatment for leukaemia, the most common blood cancer in children. However, while chemotherapy can be very effective for certain types of leukaemia, it is not as effective for some other types, known as ‘high-risk’ leukaemias. Treatment for high-risk leukaemias generally involves high doses of toxic drugs that flood the body, affecting cancer cells and healthy cells alike. This often leads to severe side effects, as well as lifelong health issues in survivors.
“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 the Children’s Cancer Institute (CCI).
“By specifically targeting leukaemia cells, we can make treatment more effective, as well as much safer to use in children.”
Specific targeting using antibodies
The new research saw scientists at CCI, UNSW and collaborating organisations use a special formulation of a cancer drug known as doxorubicin (Caelyx), in which the drug is encapsulated in tiny particles called liposomes. To this formulation, they added ‘bispecific’ antibodies — antibodies capable of recognising and attaching to the drug at one end and to cancer cells at the other end, effectively acting as a bridge between the two. Known as a targeted drug delivery system, this acts to deliver the drug to its target, in this case leukaemia cells, where the drug can do its job and kill the cells.
“What is particularly useful about this new approach is its flexibility,” said 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.”
Effective in cell and mouse models
The new approach was shown to work well not only in leukaemia cells grown in the laboratory, but also in living models of disease called ‘patient-derived xenografts’, where leukaemia cells are taken from children with the disease and grown in specially bred mice. In these models, the targeted drug delivery system was found not only to reduce the amount of leukaemia, but also to significantly prolong survival — in some cases, up to fourfold.
The researchers believe this same approach could be used to improve the selectivity of a whole range of new-generation therapeutic agents, not just chemotherapy drugs, opening the way to offering children alternative therapeutic options that are much safer than those currently on offer. They are also excited about the potential contribution it could make in the dawning era of precision medicine.
“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.
“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.
“We’ll now be working towards developing this research for clinical translation, in collaboration with our partners at [the] UNSW Australian Centre for NanoMedicine. In this study we’ve combined clinically approved drug-loaded nanoparticles with bispecific antibodies, which will help accelerate the clinical development and approval process.”
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