Lab Research

Researchers are taking a gene-focused approach to fighting disease, not just identifying cancer by the body part where it starts. This approach is called genomics.

It involves defining the cancer’s genetic profile – the set of abnormal genes (mutations) that are specific to that cancer. The abnormal genes direct how the cancer starts and grows.

Knowing the genetic profile of a specific cancer can help researchers create new treatments and guide doctors in planning the best treatment for each child.

Advances in genomics have led to new therapies and more informed treatment planning for some types of cancers. Researchers are working to expand our understanding of the genetics of many more cancers.

Genomics research at Seattle Children’s is leading to:

• Treatments that stop a critical process (biological pathway) cancer needs to grow
• More immunotherapies that target a specific protein found on the cancer’s cells and not on healthy cells. Immunotherapy uses the body’s natural infection-fighting system against cancer.
• Better ways to screen family members and help them make family planning decisions (genetic testing and counseling)
• Using genetic markers to tell whether a patient is likely to respond to certain therapies. Such markers help guide the treatment for a given patient. 

At Seattle Children’s, research teams are making advances in the genomics of these and other diseases:

• Brain tumors (Drs. Jim Olson and Sarah Leary)
• Acute myeloid leukemia (AML) (Drs. Soheil Meshinchi and Katherine Tarlock)
• Bone marrow failure disorders (Dr. Amy Geddis)

The laboratory of Dr. Jim Olson uses brain tumor tissue from patient surgeries to:

• Develop mouse models for many rare types of brain cancer.
• Create cultures of cancer stem cells – immature cancer cells that can grow into new tumors. 

The mouse model and stem cell cultures make it easier and faster to:

• Study the genetic changes in different types of brain tumors.
• Closely watch the tumors in mice to find how the cancer becomes resistant to drugs.
• Test medicines and decide which are most likely to work against cancer in people.

As a result, the most effective combination of drugs can be offered sooner in clinical trials for young people with cancer.

Dr. Jim Olson’s team is using tiny proteins (peptides) to zero in on cancer cells. The team is studying how to:

• Change peptides so they stop cancer cells from dividing and growing.
• Combine peptides with chemotherapy so the medicine is delivered mainly to cancer cells and not healthy cells.

Many peptides found in nature can be changed to fight cancer. Venom from scorpions was the model for BLZ-100 Tumor Paint. It is designed to bind to tumor cells so they glow under special laser lights in the operating room.

Tumor Paint is now being tested to see if it helps surgeons see the border between cancer and normal brain tissue. The paint was invented by a team led by Olson, a co-founder of Blaze Bioscience. The goal is to guide surgeons to remove as much cancer as possible while sparing healthy brain tissue that controls important body functions.

Dr. Richard G. Ellenbogen and partners at the University of Washington are using nanoparticles to create pinpoint therapy for brain tumors. Nanoparticles are tiny beads about 1/100,000 the diameter of a human hair. Their small size allows scientists to zoom in to the level of individual atoms and molecules. The researchers aim to deliver therapy that kills brain tumors without harming surrounding healthy tissue.

They also have made nanoparticles that can be seen with medical imaging equipment like MRI (magnetic resonance imaging) scans. Their goal is that one day doctors could see in real time if a nano-drug given to a patient with a brain tumor is working.

By analyzing hundreds of samples of brain tumor tissue donated by former patients, researchers found that certain proteins expressed by brain tumor cells are the best predictor of whether a patient’s cancer will return. Dr. Sarah Leary worked with Seattle Children’s pathologist Dr. Bonnie Cole to make that finding.

Leary and Cole have completed a clinical trial of selected therapy based on their lab work. They continue to develop new lab testing and drugs. Their goal is that each child gets treatment specific to the biology of their brain tumor.

Seattle Children's Therapeutics is creating new immunotherapies against cancer using the infection-fighting immune systems of children and young adults.

Advances in the lab have allowed researchers to genetically change a person’s T cells so the cells recognize and kill specific types of cancer cells. A team at the Ben Towne Center for Childhood Cancer and Blood Disorders Research laid the foundation for new options that are now offered to our patients in clinical trials.

Based on what they learn from these research studies, scientists are fine-tuning T-cell therapy to make it work even better. Learn more about clinical trials using T-cell immunotherapy.

The lab of Dr. Soheil Meshinchi focuses on defining the genetic makeup of childhood acute myeloid leukemia (AML). The team uses that information to:

• Develop better, personalized treatments
• Create more accurate ways to monitor disease and the effects of treatment

To personalize drug choices for young people with AML, researchers expose a child’s AML cells to hundreds of different drugs in the lab. This helps identify drugs that are likely to be most effective against that child’s AML. This type of drug testing is called “in vitro sensitivity assay.” It helps identify treatments that doctors might not have considered for that child.

Working with Dr. Soheil Meshinchi, Dr. Katherine Tarlock studies the changes in genes (mutations) that cause AML. They also look for the genetic changes that make some forms of AML high risk and harder to cure.

That understanding helps them identify children with high-risk AML and figure out new ways to treat it. For example:

• Knowing the steps that lead to overactive cell growth could help scientists block one of the steps and stop cancer from growing.
• Identifying proteins found only on AML cells would help scientists target those proteins with new therapies.

For some children with cancer or other diseases affecting their blood or immune system, treatment includes a transplant of blood-forming (hematopoietic) stem cells from a healthy donor. These are young cells that grow into different types of blood cells.

Using cells from umbilical cord blood is an option if a child does not have a stem cell donor who is a close match.

Unfortunately, cord blood has far fewer stem cells than blood or bone marrow donated by a child or adult. Because of the small number of cells, it takes much longer for the new blood and immune system to be at full strength after a transplant using cord blood.

Dr. Colleen Delaney has developed ways to greatly increase the number of stem cells in donated cord blood. The larger number of transplanted stem cells helps the child recipient recover their normal number of blood cells much sooner. This lowers the risk of life-threatening infections and other complications after transplant.

Delaney’s lab work laid the foundation for several clinical trials she is leading. All of them involve stem cell transplants using cord blood. Her new technique is based on basic science research by Dr. Irwin Bernstein.

Seattle Children’s researchers are working on new ways to do transplants so children can avoid severe or long-term graft-versus-host disease (GVHD). GVHD happens after a stem cell transplant if the new cells attack the child’s body instead of rebuilding the immune system.

Dr. Marie Bleakley has identified a subset of T cells from donor stem cells that are most likely to attack a patient’s normal cells and cause GVHD. Her lab team developed a way to remove the troublesome subset of T cells from the donor cells before transplant but keep helpful T cells. This is called “naive T-cell depletion.” The helpful T cells fight infections that often happen after transplants. The T cells also protect the child from leukemia coming back.

In the first phase 2 clinical trial using the new naive T-cell depletion method, fewer patients had GVHD than usually happens after transplantation. Patients also needed less treatment with drugs that suppress their immune systems after transplant. This means they could get immunotherapy sooner after transplant to prevent cancer from returning. Bleakley continues to study the new method.

Dr. Marie Bleakley is working to identify proteins (antigens) on leukemia cells that can be used as targets in new immunotherapy clinical trials. Her team then changes a patient’s own T cells to attack those antigens more forcefully. In the lab her team makes many copies of the patient’s modified T cells and gives them to the patient through a vein. Bleakley will test the new therapy in clinical trials to see if it helps prevent children’s cancer from coming back.

Her lab continues to find more target proteins on leukemia cells. Their goal is to create more T-cell immunotherapy options for patients who have had stem cell transplants.

Dr. Kasey Leger is working to keep hearts healthy in young people who get chemotherapy medicine to fight their cancer. She is working with Seattle Children’s cardiologists to study blood samples and echocardiograms (images of the heart) from cancer patients. The researchers look for early signs of injury to the heart and blood vessels.

If we can identify children at risk of heart damage, doctors may be able to:

• Give children medicine to protect their heart.
• Change their chemotherapy medicines or doses to avoid damage.