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For children who have cancer, chemotherapy
treatments can have a lasting impact on their health
throughout their lives. But the emerging field of
immunotherapy could offer better health outcomes for
children in the fight against cancer.
With their low toxicities, immune therapies seem
tailor-made for pediatric cancer patients where
long-term effects caused by conventional therapies
are of great concern.
Childhood cancer patients can suffer the
consequences of chemotherapy throughout their
lifetime, including fertility issues, cardiac
toxicities, learning impairment and more.
In fact, many cancer immunology experts believe
immune therapies may be a paradigm changer,
eventually replacing chemotherapy as the first-line
treatment in many pediatric cancers because of its
ability to spare patients from these dangerous
toxicities.
Take, for example, Hodgkin’s lymphoma. It is a
common childhood cancer that responds well to
chemotherapy, but treatment is long and toxic, and
the growing brains and bodies of children and
adolescents are particularly susceptible to the
damaging effects of chemotherapy.
New research shows Hodgkin’s lymphoma may be one of
the best responders so far to anti-PD-1 immune
checkpoint blockade therapy, with response rates
approaching 90 percent. There have been excellent
responses and low toxicities even in patients whose
cancer resisted standard drug treatment.
Researchers like pediatric oncologists and cancer
immunology experts Brian Ladle and Christopher
Gamper say there is emerging evidence that immune
therapies may be more effective against
chemotherapy-resistant cancer. They offer new hope
for pediatric patients with cancers that currently
cannot be cured with standard treatments.
While Ladle doesn’t think immune therapy will
completely replace the need for surgery and
chemotherapy, he believes it has great potential to
reduce the amount and duration of treatment.
More importantly, since immune cells can travel
anywhere throughout the body—inside bones and to
organs and tissues—they have a unique ability to
find and destroy lingering cancer cells that often
result in the recurrence and spread of cancers.
Ladle and Gamper are discovering crucial links
between T cell behavior, the main cells activated in
an immune response, and the epigenetic or chemical
environment of T cell DNA.
Although the DNA code of a T cell that has never
been activated is identical to that of T cells
engaged in an immune attack, significant changes
occur in the chemicals that surround the DNA that
help signal it to remain dormant or go into action.
As a result, Ladle and Gamper are deciphering the
normal epigenetic activity of immune T cells and
exploring whether existing epigenetic-targeted
treatments might be able to improve immune responses
to cancer.
Ladle and Gamper believe epigenetic drugs may
augment the effectiveness of other immune
treatments, such as cancer vaccines and immune
checkpoint blockers.
They are also looking for other proteins expressed
by tumor cells that work like PD-1 to shut down an
immune response to cancer.
In addition, new pediatric oncology
physician-scientist Nico Llosa is working on ways to
use PD-1 blockade and other similar immune agents to
fight pediatric cancers.
While there have been significant advances in cancer
immune therapies in adults over the last few years,
translating these findings to pediatric cancers lags
far behind.
For more information
Johns Hopkins Medicine
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