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In their efforts to harness a new way “to turn cancer cells into potent anticancer agents,” researchers developed a new stem cell therapy to eliminate – and prevent – brain cancer.
The therapy has shown to “eliminate established tumors and induce long-term immunity, training the immune system so that it can prevent cancer from recurring,” says Harvard University, where the study was conducted.
“Our team has pursued a simple idea: to take cancer cells and transform them into cancer killers and vaccines,” said team lead Dr. Khalid Shah, professor of neurosurgery at Harvard Medical School and Brigham and Women’s Hospital.
The researchers tested the dual-action, cancer-killing vaccine in an advanced mouse model of the deadly brain cancer glioblastoma. The results of the study, titled “Bifunctional cancer cell-based vaccine concomitantly drives direct tumor killing and anti-tumor immunity,” were published in Science Translational Medicine.
Bifunctional whole cancer cell-based therapeutic
Professor Shah’s team used living tumor cells. These can track and target tumors to develop “a bifunctional whole cancer cell–based therapeutic with direct tumor killing and immunostimulatory roles.”
The researchers “repurposed the tumor cells from interferon-β (IFN-β) sensitive to resistant using CRISPR-Cas9 by knocking out the IFN-β–specific receptor and subsequently engineered them to release immunomodulatory agents IFN-β and granulocyte-macrophage colony-stimulating factor,” the study says.
“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,” Dr. Shah explained.
The mechanism-based efficacy of engineered therapeutic tumor cells (ThTC) “translated into a survival benefit and long-term immunity in primary, recurrent, and metastatic cancer models in immunocompetent and humanized mice.
A unique approach to fighting cancer
The team notes that “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.”
Taking advantage of the unique property of living tumor cells to “travel long distances across the brain to return to the site of their fellow tumor cells,” Dr. Shah’s team tested their repurposed CRISPR-enhanced and reverse-engineered ThTCs “in different mice strains including the one that bore bone marrow, liver and thymus cells derived from humans, mimicking the human immune microenvironment.”
This built “a two-layered safety switch into the cancer cell, which, when activated, eradicates ThTCs if needed.”
Although further investigation is warranted, the study shows the science is safe, applicable, and efficacious in the used models. This suggests “a roadmap toward therapy.”
“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,” Dr. Shah said. “This therapeutic strategy is applicable to a wider range of solid tumors.”
