A biomedical physics lab at Northeastern has received a $2.7 million grant to develop a new treatment for ovarian cancer that will use lasers to locate and target chemotherapy-resistant cancer cells and boost the patient’s immune system .
“We use light to activate a cure, if you will. We also use light to interrogate a tumor,” he says Bryan Q. Springassociate professor of biomedical physics at Northeastern University.
Spring Workshopin collaboration with Heiko Enderling’s lab at MD Anderson Cancer Center and Moffitt Cancer Center, received a $2.7 million Physical Sciences Oncology Network grant from the National Cancer Institute for a research project called “Fractional photoimmunotherapy to harness low-dose immunostimulation in ovarian Cancer.”
According to the American Cancer Society, ovarian cancer causes more deaths than any other cancer of the female reproductive system. It ranks fifth in cancer deaths in women and is often diagnosed in late stages.
Women with advanced ovarian cancer currently go through a grueling treatment regimen, Spring says, that includes surgical removal of visible cancerous tumors from the pelvis or abdomen (after the affected ovaries are removed) and high-dose chemotherapy.
This standard approach often hits a wall due to drug resistance and the dose-limiting toxicity of chemotherapy. Surgeons sometimes have to leave affected areas in the abdomen for quality-of-life reasons, Spring says. An instrument can lose its function if it cuts too deeply.
“Patients really suffer from it,” he says.
Chemotherapy and surgery also cannot harness a person’s immune system to fight cancer.
“Wouldn’t it be great if you could do some chemotherapy and then activate the immune system and use the body to fight the cancer and get the immune system to be able to do what it’s supposed to do,” he says Spring. .
The awarded grant, he says, allows scientists to explore a light-activated treatment that has already been tested in pilot clinical trials, with one agent entering phase III trials. The advantage of the light-based treatment, called photodynamic therapy or photoimmunotherapy , is that in addition to killing cancer cells, it also engages and activates the immune system to pursue immunotherapy.
It may be possible to spare the “good” immune cells, even boosting their proliferation and activity to gobble up cancer cells, erasing the “bad” cancer cells that help the cancer evade the immune system, Spring says.
During treatment, antibodies that target cancer cells deliver photoactive molecules of a non-toxic chemical. When targeted with light, the chemical molecules capture its energy and toxic reactive species are created in a highly localized area that damages even chemotherapy-resistant cancer cells.
Another goal of Spring’s lab is to develop a tiny microscope that will go inside a body and interrogate a tumor using light. The device will use the power of very short pulses of light transmitted through an optical fiber for imaging.
Currently, such devices are large and unportable, Spring says, and can cost $50,000-$100,000. His lab is working to create a lightweight, portable laser device that will cost about $10,000.
“We can stain the cancer in the body and find out which proteins are available on the cell surface to target. Antibodies are then selected to target proteins expressed by the tumors that differ from the background tissue,” says Spring. “We can take advantage of this to try to deliver our photosensitizers directly to the tumor and avoid off-target damage.”
The microscope would fit into a working channel of an endoscope used by surgeons. It will be possible to obtain high-resolution images of cancer cells. By piecing these images together, Spring says, scientists can then use that information to make statistical calculations to determine what’s going on.
Research is highly interdisciplinary, he says. Designing a laser requires math and physics. Photophysics, mathematics, quantum physics, biophysics and biochemistry are behind the concepts of how the treatment works and how tissue molecules absorb photons of light and are then converted into activated species that can cause damage to cancer cells . Tumor immunology is also key to understanding biological responses to therapy.
Northeastern is the lead institution in this project that will conduct the experimental work on the treatment, Spring says. The Enderling lab will develop mathematical oncology to predict how a tumor will grow or respond to treatment.
While Spring Lab can provide unknown parameters derived from experiments to train a mathematical model, computational modeling scientists can build various models and simulate thousands of conditions that cannot be tested through experimentation.
“This helps narrow down what we really want to test in a cell culture or more advanced preclinical models,” says Spring. “Mathematical oncology really helps us guide the experiments to learn the most. And then you have a mathematical model for the community to understand.”
Alena Kuzub is a reporter for Northeastern Global News. Email her at a.kuzub@northeastern.edu. Follow her on Twitter @AlenaKuzub.
