New Antibody Decreases Bone Metastases by 100 times.

A team of scientists led by Yibin Kang and his team at Princeton University in New Jersey have created a new antibody to fight bone cancer metastases.

A team of scientists led by Yibin Kang and his team at Princeton University in New Jersey have created a
new antibody to fight bone cancer metastases.
When Cancer spreads from one location to another location, it’s called metastases. Metastases to the
bones is very difficult to treat, reverse or eliminate, in fact the most cancer deaths are from secondary
bones tumors not form the primary ones from somewhere else.
Take late-stage breast cancer for instance; about 70% have metastases to their bones, which increases
risk of fracture, pain, and other serious life-threatening events.
Once bone cancer sets in, it’s almost impossible to defeat. Treatments have to be very aggressive, have
a poor outcome, and come with many bad side-effects’ the bone cancer may even become resistant to
them.

Needless to say, a tremendous amount of time, energy and money has been devoted to cancer research
over the past decades, looking at how it develops and spreads, and how it can be curtailed or stopped.

In this case, Hanqiu Zheng lead study author, explains that the Kang Lab’s primary focus is breast cancer
metastasis, because the majority of cancer deaths is not from the original tumor but rather from
metastasis. They want to know specifically how bone cells communicate with cancer cells and what
causes that particular metastases. In that effort they have found a molecule they call “Jagged1” which
seems to be critical to the communication process that allows breast cancer cells to get to bone and grow
new tumors. Another researcher on Kang's team, Rebecca Tang, relates that they wondered if an
antibody called 15D11 could block the Jagged1, and would reduce or prevent metastases from breast to
bone.

In healthy individuals bone is removed by osteoclasts and rebuilt by osteoblasts in a constant cycle of
health and growth. Constant regeneration is essential to have healthy and fully functioning bones.
However, bone cancer, this process is disrupted. Osteoclasts destroy too much bone, and/or osteoblasts
may protect tumor cells from chemotherapy. These recent studies were interested in the role of
osteoblasts in bone metastasis at a molecular level.

"Tumors are essentially hiding in the cradles of the osteoblasts," says Kang.

They discovered that when 15D11 was given alongside chemotherapy, it worked better than either
treatment on its own. Interestingly, the team had first thought that the antibody would only work against
tumors with a high expression of Jagged1, but even those with low Jagged1 expression were reduced.

Standard chemotherapy usually stops working when Jagged1 starts being made by osteoblasts; the
tumor effectively uses Jagged1 as a shield. By specifically targeting Jagged1, 15D11 destroys this shield
and chemotherapy can continue working.

Jagged1 in a mouse model
To further investigate this relationship, Kang and his team used a genetically engineered mouse model
that expresses Jagged1 in bone cells. This strain is particularly sensitive to the growth of breast cancer in
their bones.

Experiments with the mice backed up the initial findings: mice that were treated with both 15D11 and
chemotherapy fared better than those given either treatment alone. In one experiment, the bone tumor
was reduced more than 100-fold after receiving both drugs.

"This is a remarkable response that we have never observed in any of our previous tests of therapeutic
agents against bone metastasis in mice."
Yibin Kang
Although this study only investigated breast cancer within bone, the researchers believe that this method
could work for other types of cancer that metastasize to bone, such as prostate cancer.

The next step will be to take this research to human trials. Kang hopes that this will be a relatively quick
process because 15D11 is "fully human," having been generated in a "humanized mouse."

Due to the fact that bone metastases are so difficult to treat, any new drug targets or interventions are
gratefully received. Hopefully, in the not too distant future, 15D11 will enter the ranks in the fight against
cancer.