Advances in Pediatric Tumor Analysis and Immunotherapy

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Vol. 25 No. 11 Page 16


The future is now when it comes to hematology and pediatrics.

The world of healthcare has become increasingly familiar with immunotherapy in recent years. The ability to train a patient’s immune system to fight back against malignancies has proved extremely beneficial, especially when it comes to hematologic malignancies like leukemia. However, should medical laboratory professionals soon expect an expansion of the use of immunotherapy in pediatrics?

Indeed, some clinical laboratories have already begun to explore the possibilities of using immunotherapy to combat pediatric tumors—and for good reason. “Some cancers are better at evading the immune system and escaping detection than others,” said Gregory Friedman, MD, associate professor of pediatric hematology and oncology at the University of Alabama at Birmingham. “Different tumor types can express immunosuppressive proteins in varying amounts which can lead to some cancers being more sensitive than others to immunotherapy.”

Explorations in Immunotherapy
Although immunotherapy certainly holds promise for treating pediatric cancer, its use is still in trial stages, typically in patients with recurrent disease. Once those trials move further along, however, Friedman anticipates that it will be used alongside other treatments such as conventional chemotherapy and radiation, various targeted drugs or even other immunotherapies.

The trials that are taking place have already paved the way for this progress. Friedman’s own research has focused on the use of engineered oncolytic herpes virotherapy to target pediatric brain tumors, which are typically harder for immune cells to target.

“Herpes virus has been engineered to be safe for normal cells but can infect and kill cancer cells and can stimulate the patient’s own immune system to attack the cancer,” Friedman explained. “A human cytokine gene, such as interleukin-12, can be added to the virus so that when the virus replicates, it produces the cytokine which stimulates an even more robust anti-tumor immune response.” To further explore the possibilities of this therapy, this year, Friedman initiated the first pediatric trial of engineered herpes virus G207 in children with current or progressive brain tumors.1

However, this is not the only research on the use of immunotherapy with pediatric cancers. Cathy Lee-Miller, MD, staff physician of the Center for Cancer and Blood Disorders at Phoenix Children’s Hospital, has become familiar with the use of dinutuximab and chimeric antigen receptor T (CAR T) cells to fight against these malignancies. “We’ve started to use dinutuximab, a generic 14.18 monoclonal antibody that has been used in trials for high-risk neuroblastomas, and there’s a trial now that’s using dinutuximab in cases of relapse for osteosarcoma,” Lee-Miller shared. “Right now, CAR T cells are exclusively being used for acute lymphoblastic leukemia in children, but that model is expanding. I think that in the future, we’ll see it used for other types of leukemias as well as lymphomas and potentially solid tumors as well.”

“I believe that immunotherapy is how all cancers will be treated in the future,” Friedman agreed. “Conventional therapies are very damaging to a developing child, and often survivors suffer from lifelong side effects from current therapies. Harnessing the child’s own immune system to fight off the tumor or even keep the tumor from growing is an ideal treatment approach.”

The Future of Diagnostics
Hematology is crucial when it comes to pediatric cancers in more areas than treatment. Tumor marker tests can be a critical part of identifying and tracking cancers, especially in young children. “For example, alpha-fetoprotein is extremely helpful in following a case of hepatoblastoma,” said Lee-Miller. “Being able to see those numbers can be the best way of knowing what’s going on. You can’t put a child through a CT or an MRI scan on a weekly basis, but you can certainly perform a blood test.”

Alpha-fetoprotein (AFP) can be elevated in a multitude of different cancers, particularly in those affecting children. Currently, according to Lee-Miller, the other primary option for tumor marker tests is beta human chorionic gonadotropin (beta HCG), which is elevated in certain germ cell tumors.

Although these tests are extremely beneficial in identifying and monitoring pediatric tumors, at this point, they cannot be used alone to diagnose. “There are very few instances in which a blood test is the only test you need in order to diagnose a cancer in a child,” said Lee-Miller. “It has to be used with other tests, biopsies, in order to make a definitive diagnosis.”

Still, Lee-Miller knows how crucial these tests are in diagnosing pediatric cancers and has hope for the future of tumor marker tests. “I think that, to a certain extent, we’ll never get away from using some of these tumor markers,” she said. “I think blood tests will really always be a part of caring for and monitoring certain diseases in children. I don’t know what the future holds, but I hope we’ll have more blood markers for different diseases because it gives us another piece of information that we don’t have in other types of malignancies.”

References

  1. gov. HSV G207 alone or with a single radiation dose in children with progressive or recurrent supratentorial brain tumors. Available at: https://clinicaltrials.gov/ct2/show/NCT02457845
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Sarah Sutherland
Sarah Sutherland

Sarah Sutherland is a staff writer at ADVANCE. Contact: ssutherland@advanceweb.com

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