A revolutionary cancer vaccine kills and prevents brain tumors at the same time
The dual-action cell therapy is designed to eliminate existing tumors and train the immune system to eradicate the primary tumor and prevent the cancer from recurring.
Scientists are using a new way to turn cancer cells into powerful anti-cancer agents. In the latest work from the laboratory of Khalid Shah, MS, PhD, at Brigham and Women’s Hospital, founder of the Mass General Brigham Health System, researchers have developed a new approach to cell therapy to eliminate existing tumors and promote 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 glioblastoma brain cancer, with promising results. The findings were published in Science 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 research in the Department of Neurosurgery. at Brigham and Harvard Medical School and the Harvard Stem Cell Institute (HSCI). “Using genetic engineering, we repurpose cancer cells to develop a drug that kills tumor cells and stimulates the immune system to destroy primary tumors and prevent cancer.”
Cancer vaccines are an active area of research for many labs, but the approach taken by Shah and his colleagues is different. Instead of using inactivated tumor cells, the team is repurposing living tumor cells, which possess an unusual feature. Like pet pigeons returning to the 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 gene-editing tool CRISPR-Cas9 and re-engineered them to release a tumor-killing agent. In addition, the engineered tumor cells were designed to express factors that would make it easier for the immune system to spot, tag, and remember them, priming the immune system for a long-term antitumor 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 double-layer safety switch into the cancer cell that, when activated, eradicates TTCs if needed. This dual-acting cellular therapy was safe, applicable, and effective in these models, suggesting a plan toward therapy. Although further testing and development is needed, Shah’s team specifically chose this model and used human cells to ease the path to translating their findings to patient settings.
“Through all the work we do at the Center, even when it’s very technical, we never lose sight of the patient,” Shah said. “Our goal is to take an innovative yet translatable approach so that we can develop a therapeutic cancer vaccine that will ultimately have lasting impact in medicine.” Shah and colleagues note that this therapeutic strategy is applicable to a wider range of solid tumors and that further research into its application is warranted.
Reference: “A bifunctional cancer cell-based vaccine simultaneously promotes direct tumor killing and antitumor immunity” Kok-Siong Chen, Clemens Reinshagen, Thijs A. Van Schaik, Filippo Rossignoli, Paulo Borges, Natalia Claire Mendonca, Reza Abdi, Brennan Simon, David A .Reardon, Hiroaki Wakimoto and Khalid Shah, 4 Jan 2023, Science translational medicine.
Disclosures: Shah owns stock 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).