The National Cancer Institute’s Rosandra N. Kaplan, MD, breaks down her research on altering myeloid cell’s injury repair response to better attack osteosarcoma.
Rosandra N. Kaplan, MD, a pediatric oncologist, physician scientist, and a senior investigator of the Pediatric Oncology Branch at the National Cancer Institute, is on a mission to prevent tumor metastasis, which is the leading cause of cancer-related deaths. Her approach is to take an element of the tumor’s microenvironment that typically enables tumor growth and reprogram it to attack metastatic cancer.
This is the second part of a two-part Frontline series focusing on Dr. Kaplan’s work. Part one explores the role of the tumor microenvironment in enabling tumor growth. Part two examines Dr. Kaplan’s research attempting to design new osteosarcoma therapies.
Why Myeloid Cells?
Dr. Kaplan’s experimental cancer therapy involves myeloid cells, a part of the body’s immune system that responds to infection or injury. When myeloid cells detect damage, they travel through the bloodstream to rally other cells to the area. She calls them the moms of the immune system because they are the first and last to handle any problem.
“If you ask any pathologist to stain an osteosarcoma for the myeloid cells, they are hugely abundant,” Dr. Kaplan says. Normally, myeloid cells interpret osteosarcoma as an injury that needs to be healed, so they send messages to T-cells to quiet down, inadvertently fueling cancer’s growth.
“If you ask any pathologist to stain an osteosarcoma for the myeloid cells, they are hugely abundant. We can’t beat them, so we have to join them.” — Rosandra N. Kaplan, MD
Since myeloid cells play a role in cancer growth, it might seem tempting to try to eliminate them altogether. But these cells are crucial to the body’s functioning, Dr. Kaplan says. “We can’t beat them, so we have to join them.”
A Delicate Balance
Genetically engineered myeloid cells (GEMys). Photo courtesy of Rosandra N. Kaplan, MD.
“We know myeloid cells are able to activate T-cells,” Dr. Kaplan explains. In the setting of infection, myeloid cells instruct T-cells to fight infection by secreting a cytokine called interleukin 12, or IL-12 for short. A cytokine is a protein made by cells to communicate with the immune cells. Some, like IL-12, can stimulate the immune system, and others can slow it down. Dr. Kaplan’s genetically engineered myeloid cells will secrete IL-12 near T-cells to instruct them to attack tumors such as osteosarcoma.
Engineering the patient’s own myeloid cells solves the problem of getting the IL-12 to the right locations. “Delivering IL-12 on its own through the bloodstream is toxic,” Dr. Kaplan explains. “You only want a few cells to see the IL-12, not all of them. The myeloid cells should be secreting it near the T-cell. They should be talking like they are having a coffee at a Starbucks.”
Preventing Recurrence
The timing is important, too: Dr. Kaplan hopes to deliver the genetically engineered myeloid cells after a patient has completed surgery to prevent a recurrence. “We have a lot of patients that are what we call NED — no evidence of disease. They have gotten their primary tumor or metastatic tumor removed and they sit with the fear that it is going to come back.” This is when she wants to educate their T-cells to be prepared to attack any new osteosarcoma.
In Dr. Kaplan’s vision, genetically engineered myeloid cells would be just one component of the therapy osteosarcoma patients would receive. Dr. Kaplan’s lab is also researching other potential cancer therapies that could address the stromal cells and extracellular matrix, which are both important in bone cancer metastasis.
Rosandra N. Kaplan, MD
If the research continues to be promising, Dr. Kaplan hopes to begin delivering genetically modified myeloid cell therapy to patients in a few years. The endgame is to develop additional osteosarcoma treatments beyond MAP, the standard regimen of chemotherapy, which can be tough on patients especially if their cancer comes back and they need to receive more chemotherapy. Dr. Kaplan has seen osteosarcoma patients suffer shortened lifespans or develop new cancers because of the chemotherapy they received in treatment. If there were additional options to prevent the immune system and extracellular matrix from protecting the cancer, this could help lessen the chemotherapy patients receive.
“The Osteosarcoma Institute is helping to elevate the entire research space,” she says. “The OSI is making osteosarcoma more well-known on the map, helping families talk to one another, and bringing together the osteosarcoma research community.”
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