Selective targeting of cancer cells in new therapeutic approaches

Scientists in Australia have developed a new way to solve a decades-old clinical problem by targeting therapeutic drugs to target cancer cells in the body.

It was published in the magazine scientific translational medicinethe team’s research paves the way for safer and more effective treatment options for children with advanced blood cancers, and potentially other types of cancer.

Chemotherapy is the mainstay of treatment for leukemia, the most common blood cancer in children. However, while chemotherapy is very effective against certain types of leukemia, it is less effective against other types known as “high-risk” leukemia. Treatment of high-risk leukemia typically involves administering large doses of toxic drugs into the body, which affect both cancer cells and healthy cells. This often causes serious side effects and lifelong health problems in survivors.

“Finding ways to make therapeutic agents more selective to cancer cells is key to improving treatment success rates while reducing toxicity in children treated for high-risk leukemia,” said lead investigator Maria.・ Professor Kavalaris AM said: Medicine and Health in New South Wales and the Pediatric Cancer Research Institute (CCI).

“By specifically targeting leukemic cells, we can make treatments more effective and safer for pediatric use.”

Specific targeting using antibodies

In this new study, CCI scientists New South Wales And the cooperating organization uses a special formulation of an anticancer drug known as doxorubicin (Caelyx), which is encapsulated in tiny particles called liposomes. To this formulation they added a “bispecific” antibody. This is an antibody that can recognize a drug on one end and a cancer cell on the other end and bind to it, effectively acting as a bridge between the two. This system, known as a targeted drug delivery system, works to deliver a drug to a target, in this case a leukemic cell, where the drug can work and kill the cell.

“What makes this new approach particularly useful is its flexibility,” said lead author Dr. Ernest Moles of UNSW Medicine & Health and CCI.

“We can use this system to target any type of leukemia, including the high-risk subtypes that kill Australian children every year, without having to design a whole new treatment every time. , the same drug could be targeted to any pediatric hematological cancer simply by altering the cross-linking of the antibody.

“Furthermore, this approach has the potential to counteract drug resistance in individual patients. If pediatric cancer cells attempt to evade chemotherapy by altering their cell surface, we can modify the targeted drug delivery system. , can make the altered cancer cells recognizable.It won’t be able to escape easily.”

Effective in cell and mouse models

This new approach works not only with leukemia cells grown in the laboratory, but also with a living model of the disease called “patient-derived xenografts,” in which leukemic cells are taken from sick children and grown in specially bred mice. shown to work well. In these models, targeted drug delivery systems not only reduced leukemia burden, but also significantly increased survival (up to 4-fold in some cases).

Researchers believe that this same approach could be used to improve the selectivity of not just chemotherapy drugs, but any new generation of therapeutics, offering far safer alternative treatment options than those currently offered. I think it will open the way to provide for children. They are also excited about its potential contribution in the early days of precision medicine.

“In the future, each child diagnosed with leukemia may be able to receive targeted treatment for a specific subtype based on the analysis of blood samples,” Kavalaris said. said.

“We believe the controlled targeting of nanotherapeutics is a true milestone in the treatment of childhood cancers, and we are very optimistic about what this will bring.

“We will continue to work with partners to develop this study for clinical translation. [the] New South Wales Australian Nanomedicine Center. In this study, we combined clinically approved drug-loaded nanoparticles with bispecific antibodies. This helps accelerate the clinical development and approval process. “

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