Hybrid Leukemia Therapy May Boost Treatment Options

A new hybrid treatment has been developed that harnesses a monoclonal antibody to deliver antisense DNA to acute lymphoblastic leukemia (ALL) cells, and may lead to less toxic and improved treatment options in the future.

ALL is the most common form of pediatric cancer, and although most children are able to survive the disease, many patients suffer late or long-term side effects from treatment. These may include growth and development delays, secondary cancers, infertility, and heart problems.

In a study published in Molecular Medicine, researchers sought to minimize some of the negative side effects that occur in ALL patients by developing a novel conjugate therapy. Antisense oligonucleotides are single strands of DNA that can bind to messenger RNA to prevent it from making a protein.

Although, antisense technology has shown therapeutic potential, there has been issues with getting genetic material inside the target cells. During the experiment, researchers attached antisense DNA that inhibits the MXD3 protein to an antibody that binds to CD22.

The results of the study showed that once the binding occurred, the conjugate was drawn inside of the leukemia cell, allowing the antisense molecule to prevent MXD3 production. When the anti-apoptotic protein was removed, the ALL cells were more prone to cell death.

“We’ve shown, for the first time, that anti-CD22 antibody-antisense conjugates are a potential therapeutic agent for ALL,” said researcher Noriko Satake. “This could be a new type of treatment that kills leukemia cells with few side effects.”

Researchers found that the hybrid treatment was effective against the ALL cell lines in vitro, and the primary ALL cells in a xenograft mouse model. Additionally, animals administered the hybrid therapy were found to survive significantly longer than those in the control group.

The hybrid treatment was designed to only target cells that express CD22, and to leave blood stem cells and other tissues alone.

“You really don’t want to destroy hematopoietic stem cells because then you have to do a stem cell transplant, which is extremely intensive therapy,” Satake said. “Our novel conjugate is designed so that it does not harm hair, eyes, heart, kidneys or other types of cells.”

Authors noted that although the findings demonstrated the conjugate knocked down MXD3, the mechanisms of how this was accomplished still needs to be found. Furthermore, they plan to see how the treatment performs when combined with other therapies, and how it works against other forms of cancer.

“You can see this as a proof of principle. You could switch the target and substitute the antibody, which could be used to treat other cancers or even other diseases,” Satake said.