Researchers at Brigham and Women’s Hospital have developed a novel treatment that reprograms cancer cells into tumor-killing agents.
The new vaccine showed positive results in a mouse model of advanced glioblastoma, a deadly cancer of the brain. It was found to simultaneously eliminate current tumors and prevent tumor recurrence.
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More than 13,000 people in America were diagnosed with this brain cancer type in 2022, according to experts. Research also suggests that its incidence is on the rise.
“Our team has pursued a simple idea: to take cancer cells and transform them into cancer killers and vaccines,” said Dr. Khalid Shah, study corresponding author and director of the Center for Stem Cell and Translational Immunotherapy (CSTI) at Brigham and Women’s Hospital. “Using gene engineering, we are repurposing cancer cells to develop a therapeutic that kills tumor cells and stimulates the immune system to destroy primary tumors and prevent cancer.”
Study results were published in the journal Science Translational Medicine.
Cancer vaccines
Researchers have been devoting more time toward developing cancer vaccines in recent years. Like other vaccines, these are intended to help the immune system develop the ability to detect and destroy cells that could cause problems in the body.
Cancer vaccines that are currently being worked on by researchers fall into two major categories in terms of how they work. Some are aimed at keeping cancer from occurring while others treat existing cancer and prevent it from recurring.
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The approach that Shah and his fellow researchers adopted for their cancer vaccine work is different from that of other labs doing similar work. Their research does not center on the use of inactivated tumor cells. They instead repurpose living tumor cells, which have a distinctive ability to target tumors.
The team developed a cell-based bifunctional therapeutic strategy that involves the changing of living tumor cells into powerful anti-cancer agents. Using the CRISPR-Cas9 gene editing tool, the researchers engineered living tumor cells to release substances that kill tumor cells.
Shah and his colleagues also ensured that the engineered tumor cells express factors that would enable easy detection and tagging by the immune system. This can go a long way to ensure a strong anti-tumor response by the immune system in the long term.
Killing and preventing tumors
The research team put their reverse-engineered, repurposed therapeutic tumor cells (ThTC) in diverse strains of mice. These strains included one with liver, bone marrow, and thymus cells from humans and so mimicked the immune microenvironment of humans.
The mouse models showed that this cell therapy was not only effective but also safe. A two-layered safety switch was built into cancer cells to enable the removal of ThTCs if necessary.
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This treatment was also found to be applicable and showed promise as a therapy for humans. The researchers purposely chose the particular model and included human cells with the translation of their findings to human patients in mind.
“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,” Shah explained.
The researchers pointed out that the potential usefulness of their dual-action cell therapy is not limited to glioblastoma. It could also help to treat a wide range of other tumors.
Meanwhile, more work has to be done by researchers to turn this work into a proof-of-concept in humans. There is optimism that this kind of cancer vaccine could become available for public use in less than five years.
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