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Revolutionary cancer vaccine both kills and prevents brain tumors

Revolutionary cancer vaccine both kills and prevents brain tumors

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Researchers at Brigham and Women’s Hospital have discovered a way to use cancer cells to fight cancer. In a study published in Scientific Translational Medicine, the team led by Khalid Shah demonstrated that their cell therapy could eliminate established tumors and create long-term immunity in an advanced mouse model of glioblastoma, a type of brain cancer. The vaccine works by training the immune system to prevent the cancer from returning. These results are encouraging and suggest that this approach may be effective in treating cancer in humans.

A dual action cell therapy designed to eliminate established tumors and train the immune system to eradicate the primary tumor and prevent cancer from recurring.

Scientists are using a new way to turn cancer cells into powerful anti-cancer agents. In recent work from the lab of Khalid Shah, MS, PhD, at Brigham and Women’s Hospital, a founding member of the Mass General Brigham Health System, researchers have developed a new cell therapy approach to eliminate established tumors and induce long-term immunity, training the immune system so 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. The findings are published in Scientific Translational Medicine.

“Our team pursued a simple idea: 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 vice chair of the research in the Department of Neurosurgery at Brigham and faculty at Harvard Medical School and the Harvard Stem Cell Institute (HSCI). “Using genetic engineering, we are rewiring cancer cells to develop a therapeutic that kills tumor cells and stimulates the immune system to both destroy primary tumors and prevent cancer.”

A double-acting cancer-killing vaccine

Scientists have developed a bifunctional therapeutic strategy by transforming living tumor cells into therapeutic ones. Shah’s team engineered living tumor cells using the CRISPR-Cas9 gene-editing tool and re-engineered them to release a tumor-cell-killing agent. In addition, the engineered tumor cells were engineered 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 strains of mice, including one bearing human-derived bone marrow, liver and thymus cells, mimicking the human immune microenvironment. Shah’s team also built a two-layer safety switch in the cancer cell that, when activated, destroys ThTCs as needed. Credit: Kok Siong Chen and Khalid Shah

Cancer vaccines are an active area of ​​research for many labs, but the approach Shah and his colleagues have taken is different. Instead of using inactivated tumor cells, the team re-used living tumor cells that possessed an unusual characteristic. Like homing pigeons returning to roost, living tumor cells will travel long distances through 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 CRISPR-Cas9 gene-editing tool and re-engineered them to release a tumor-cell-killing agent. In addition, the engineered tumor cells were engineered 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 strains of mice, including one bearing human-derived bone marrow, liver and thymus cells, mimicking the human immune microenvironment. Shah’s team also built a two-layer safety switch in the cancer cell that, when activated, destroys ThTCs as needed. This dual-action cell therapy is safe, applicable, and efficacious in these models, suggesting a roadmap to therapy. Although further testing and development is needed, Shah’s team specifically chose this model and used human cells to ease the path of translating their findings to patient settings.

“Throughout all the work we do at the Center, even when it’s highly technical, we never lose sight of the patient,” Shah said. “Our goal is to take an innovative yet translational approach so that we can develop a therapeutic cancer-killing vaccine that will ultimately have a lasting impact in medicine.” Shah and colleagues note that this therapeutic strategy is applicable to more a wide range of solid tumors and that further research into its applications is warranted.

Reference: “A Bifunctional Cancer Cell-Based Vaccine Simultaneously Stimulates Direct Tumor Killing and Antitumor Immunity” by Kok-Siong Chen, Clemens Reinshagen, Thijs A. Van Schaik, Filippo Rossignoli, Paulo Borges, Natalia Claire Mendonca, Reza Abdi , Brennan Simon, David A. Riordan, Hiroaki Wakimoto, and Khalid Shah, 4 Jan. 2023, Scientific Translational Medicine.
DOI: 10.1126/scitranslmed.abo4778

Disclosures: Shah owns equity and serves on the board of directors of AMASA Therapeutics, a company developing stem cell-based cancer therapies.

Funding: This work was supported by the National Institutes of Health (grant R01-NS121096).




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