A cancer vaccine to simultaneously kill and prevent brain cancer


Scientists are harnessing a new way to turn cancer cells into potent, anti-cancer agents. In the latest work, 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. “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.”

Cancer vaccines are an active area of research for many labs, but the approach that the researchers 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, the 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.

The team also built a two-layered safety switch into the cancer cell, which, when activated, eradicates ThTCs 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 is needed, the team specifically chose this model and used human cells to smooth the path of translating their findings for patient settings.

https://www.science.org/doi/10.1126/scitranslmed.abo4778

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