Researchers at Brigham and Women’s Hospital have discovered a way to use cancer cells to fight cancer. In a study published in Science Translational Medicine, a team led by Khalid Shah demonstrated that cell therapy can eliminate established tumors and create long-term immunity in an advanced mouse model of glioblastoma, a type of brain tumor. It works by training the immune system to prevent These results are encouraging and suggest that this approach may be effective in treating human cancers.
A dual-acting cell therapy designed to eliminate established tumors, train the immune system to eradicate the primary tumor, and prevent cancer recurrence.
Scientists are using new methods to turn cancer cells into powerful anticancer drugs. In a recent study from the lab of Khalid Shah, MS, PhD, Brigham and Women’s HospitalA founding member of the Mass General Brigham Health Care System, the team tested a dual-acting, cancer-killing vaccine in an advanced mouse model of the deadly glioblastoma of the brain with promising results. Result is, Science Translational Medicine.
“Our team has pursued a simple idea: take cancer cells and transform them into cancer cells and vaccines,” says the Center for Stem Cell and Translational Immunotherapy. (CSTI) Director and Vice-Chair and Corresponding Author Khalid Shah, MS, PhD. He is on the faculty of Brigham University Neurosurgery, Harvard Medical School and Harvard Stem Cell Institute (HSCI). “We are using genetic engineering to develop therapies that repurpose cancer cells to kill tumor cells, stimulate the immune system to destroy primary tumors, and prevent cancer.”
Scientists have developed a bifunctional therapeutic strategy by converting living tumor cells into therapeutic agents. Shah’s team used the gene-editing tool CRISPR-Cas9 to manipulate living tumor cells and reuse them to release a tumor-cell-killing agent. In addition, engineered tumor cells are designed to express factors that enable the immune system to easily discover, tag and remember, priming the immune system for long-term anti-tumor responses. . The team has developed repurposed, CRISPR-enhanced and reverse-engineered therapeutic tumor cells (ThTCs) in a variety of mouse strains, including those that yield human-derived bone marrow, liver, and thymocytes that mimic the human immune microenvironment. ) was tested. Shah’s team also incorporated his two-layer safety switch into cancer cells. When this switch is activated, he will eradicate ThTC if necessary. Credits: Kok Siong Chen and Khalid Shah
Cancer vaccines are an area of active research in many laboratories, but the approach taken by Shah and his colleagues is unique. Instead of using inactivated tumor cells, the team reuses live tumor cells with abnormal characteristics. Like a homing pigeon returning to its roost, live tumor cells travel long distances in the brain to return to the location of their fellow tumor cells. Taking advantage of this unique property, Shah’s team manipulated living tumor cells using the gene-editing tool CRISPR-Cas9 and repurposed them to release tumor cell killing agents. Additionally, genetically engineered tumor cells are designed to express factors that enable the immune system to easily discover, tag, and remember, priming the immune system for long-term anti-tumor responses. increase.
The team has developed repurposed, CRISPR-enhanced and reverse-engineered therapeutic tumor cells (ThTCs) in a variety of mouse strains, including those that yield human-derived bone marrow, liver, and thymocytes that mimic the human immune microenvironment. ) was tested. Shah’s team also incorporated his two-layer safety switch into cancer cells. When this switch is activated, he will eradicate ThTC if necessary. This dual-acting cell therapy is safe, applicable, and effective in these models, suggesting a roadmap to therapy. Further testing and development is needed, but Shah’s team specifically chose this model and used human cells to smooth the way for translating their findings into the patient setting.
“Throughout everything we do at the center, we never lose sight of our patients, even if they are highly technical,” says Shah. “Our goal is to employ innovative yet translatable approaches that will ultimately allow us to develop therapeutic cancer-killing vaccines that will have a lasting impact on medicine.” Shah. and colleagues note that this therapeutic strategy is applicable to a broader range of solid tumors, requiring further investigation of its application.
See also: “A bifunctional cancer cell-based vaccine promotes direct tumor killing and anti-tumor immunity simultaneously,” 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, Khalid Shah, 4 January 2023, Science Translational Medicine.
DOI: 10.1126/scitranslmed.abo4778
Disclosure: Shah is an equity owner and member of the board of directors of AMASA Therapeutics, a company developing stem cell-based therapies for cancer.
Funding: This work was supported by the National Institutes of Health (Grant R01-NS121096).
