Breakthrough cancer vaccine simultaneously kills and prevents brain cancer
[Jan.13, 2022: Serena Bronda, Brigham and Women's Hospital]
Dual-action cell therapy engineered to eliminate established tumors and train the immune system to eradicate primary tumor and prevent cancer’s recurrence. (CREDIT: Creative Commons)
Scientists are harnessing a new way to turn cancer cells into potent, anti-cancer agents. In the latest work from the lab of Khalid Shah, MS, PhD, at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, 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.
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 Khalid Shah, MS, PhD, director of the Center for Stem Cell and Translational Immunotherapy (CSTI) and the vice chair of research in the Department of Neurosurgery at the Brigham and faculty at Harvard Medical School and Harvard Stem Cell Institute (HSCI).
“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”, he continued.
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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 tumor cell killing agent. In addition, the engineered tumor cells were designed to express factors that would make them easy for the immune system to spot, tag and remember, priming the immune system for a long-term anti-tumor response.
The team tested their repurposed CRISPR-enhanced and reverse-engineered therapeutic tumor cells (ThTC) in different mice strains including the one that bore 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 ThTCs if needed.
Scientists developed a bifunctional therapeutic strategy by transforming living tumor cells into a therapeutic. (CREDIT: Kok Siong Chen and Khalid Shah)
This dual-action cell therapy was safe, applicable, and efficacious in these models, suggesting a roadmap toward therapy. While further testing and development is needed, Shah’s team specifically chose this model and used human cells to smooth the path of translating their findings for patient 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.”
ThTC promotes apoptosis in the resection cavity of immunodeficient mice. Representative immunofluorescence staining images showing c-Caspase3+ cells in the resection cavity of NOD SCID mice. (CREDIT: Science Translational Medicine)
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.
How common are brain tumors, and are they dangerous?
In the United States, brain and nervous system tumors affect about 30 adults out of 100,000. Brain tumors are dangerous because they can put pressure on healthy parts of the brain or spread into those areas. Some brain tumors can also be cancerous or become cancerous. They can cause problems if they block the flow of fluid around the brain, which can lead to an increase in pressure inside the skull. Some types of tumors can spread through the spinal fluid to distant areas of the brain or the spine.
Brain Tumor Symptoms
According to Johns Hopkins Medicine, different parts of the brain control different functions, so brain tumor symptoms will vary depending on the tumor’s location. For example, a brain tumor located in the cerebellum at the back of the head may cause trouble with movement, walking, balance and coordination. If the tumor affects the optic pathway, which is responsible for sight, vision changes may occur.
The tumor’s size and how fast it’s growing also affect which symptoms a person will experience.
In general, the most common symptoms of a brain tumor may include:
Headaches
Seizures or convulsions
Difficulty thinking, speaking or finding words
Personality or behavior changes
Weakness, numbness or paralysis in one part or one side of the body
Loss of balance, dizziness or unsteadiness
Loss of hearing
Vision changes
Confusion and disorientation
Memory loss
Brain Tumor Causes and Risk Factors
Doctors don’t know why some cells begin to form into tumor cells. It may have something to do with a person’s genes or his or her environment, or both. Some potential brain tumor causes and risk factors may include:
Cancers that spread from other parts of the body
Certain genetic conditions that predispose a person to overproduction of certain cells
Exposure to some forms of radiation
Are brain tumors hereditary?
Genetics are to blame for a small number (fewer than 5%) of brain tumors. Some inherited conditions put individuals at greater risk of developing tumors, including:
Neurofibromatosis
Von Hippel-Lindau disease
Li-Fraumeni syndrome
Familial adenomatous polyposis
Lynch syndrome
Basal cell nevus syndrome (Gorlin syndrome)
Tuberous sclerosis
Cowden syndrome
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Note: Materials provided above by Brigham and Women's Hospital. Content may be edited for style and length.
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