Malignant cancer cells. Image: koto_feja/ Getty Images E+ Collection
Scientists are harnessing a new way to turn cancer cells into potent anticancer agents.
In the latest work from the lab of Khalid Shah, professor of neurosurgery at Harvard Medical School and Brigham and Women's Hospital, investigators have developed a new cell therapy approach to eliminate established tumors and induce long-term immunity, training the immune system so that it can prevent cancer from recurring.
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In this early research, the team tested their dual-action, cancer-killing vaccine in an advanced mouse model of the deadly brain cancer glioblastoma, with promising results. Findings are published in Science Translational Medicine.
“Our team has pursued a simple idea: to take cancer cells and transform them into cancer killers and vaccines,” said corresponding author Shah, who is also director of the Center for Stem Cell and Translational Immunotherapy and vice chair of research in the Department of Neurosurgery at Brigham and Women’s as well as a faculty member at the Harvard Stem Cell Institute.
“Using gene engineering, we are repurposing cancer cells to develop a therapeutic that kills tumor cells and stimulates the immune system to both destroy primary tumors and prevent cancer,” Shah said.
Cancer vaccines are an active area of research for many labs, but the approach that Shah and his colleagues have taken is distinct. Instead of using inactivated tumor cells, the team repurposes living tumor cells, which possess an unusual feature.
Like homing pigeons returning to roost, living tumor cells will travel long distances across the brain to return to the site of their fellow tumor cells. Taking advantage of this unique property, Shah’s team engineered living tumor cells using the gene editing tool CRISPR-Cas9 and repurposed them to release a tumor cell killing agent.
In addition, the engineered tumor cells were designed to express factors that would make it easy for the immune system to spot, tag, and remember them, priming the immune system for a long-term antitumor response.
The team tested their repurposed CRISPR-enhanced and reverse-engineered therapeutic tumor cells in different mice strains, including one that contained bone marrow, liver, and thymus cells derived from humans, mimicking the human immune microenvironment.
Shah’s team also built a two-layered safety switch into the cancer cell, which, when activated, eradicates therapeutic tumor cells if needed. This dual-action cell therapy was safe, applicable, and efficacious in these models, suggesting a roadmap toward therapy.
While further testing and development are needed, Shah’s team specifically chose this model and used human cells to smooth the path of translating their findings for clinical settings.
“Throughout all of the work that we do in the center, even when it is highly technical, we never lose sight of the patient,” said Shah.
“Our goal is to take an innovative but translatable approach so that we can develop a therapeutic, cancer-killing vaccine that ultimately will have a lasting impact in medicine,” he said.
Shah and colleagues note that this therapeutic strategy is applicable to a wider range of solid tumors and that further investigations of its applications are warranted.
By HALEY BRIDGER | Brigham and Women's Hospital
