Dual-action cell therapy is designed to kill existing tumors, train the immune system to eradicate the initial tumor, and prevent the cancer from recurring.
Scientists harness a new way to turn cancer cells into powerful anti-cancer agents. In the latest work from the laboratory of Khalid Shah MA Phd in Brigham and Women’s HospitalA founding member of Mass Brigham Healthcare, the investigators developed a novel cell therapy approach to eradicate stable tumors and stimulate immunity over the long term, training the immune system so it can prevent cancer from recurring. The team tested their dual-acting, cancer-killing vaccine in an advanced mouse model of the fatal brain cancer of glioblastoma, with promising results. The results are published in Translational Medicine Sciences.
“Our team pursued a simple idea: take cancer cells and turn them into cancer killers and vaccines,” said corresponding author Khalid Shah, PhD, director of the Center for Stem Cells and Translational Immunotherapy (CSTI) and vice president. From research in Brigham’s Department of Neurosurgery and faculty at Harvard Medical School and the Harvard Stem Cell Institute (HSCI). “Using gene engineering, we repurpose cancer cells to develop a treatment that kills cancer cells and stimulates the immune system to destroy primary tumors and prevent cancer.”
Cancer vaccines are an active area of research for many laboratories, but the approach taken by Shah and his colleagues is distinct. Instead of using inactivated cancer cells, the team reused live cancer cells, which have an unusual advantage. Like homing pigeons returning to their roost, live cancer cells travel long distances through the brain to return to the site of other cancer cells. Taking advantage of this unique property, Shah’s team engineered living tumor cells with the gene-editing tool CRISPR-Cas9 and redirected them to release the cancer cell-killing factor. In addition, engineered cancer cells were designed to express factors that would make it easier for the immune system to detect, label, and remember them, primed the immune system for a long-term anti-tumor response.
The team tested CRISPR-enhanced, reverse-engineered therapeutic tumor cells (ThTC) in different mouse strains including those carrying human-derived bone marrow, liver and thymus cells, which mimic the human immune microenvironment. Shah’s team also built a bilayered safety switch into the cancer cell that, when activated, knocks out ThTCs if needed. This double-acting cell therapy was safe, viable, and effective in these models, suggesting a roadmap toward a cure. While more testing and development is needed, Shah’s team chose this particular model and used human cells to facilitate the path of translating their findings for patient settings.
“Throughout 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 but translatable approach so that we can develop a therapeutic vaccine to kill cancer that will eventually have a lasting impact in medicine.” Shah and colleagues note that this therapeutic strategy is applicable to a wider range of solid tumors and that further investigations of its applications are warranted.
Reference: “Tumor Cell-Based Bifunctional Vaccine Concomitantly Induces Direct Tumor Killing and Antitumor Immunity” Written by Kok Seung Chen, Clemens Renshagen, Tijs A. Van Schaik, Filippo Rossignoli, Paolo Borges, Natalia Claire Mendonca, Reza Abdi, Brennan Simon, David Reardon, Hiroaki Wakimoto and Khalid Shah, January 4, 2023, Translational Medicine Sciences.
Disclosures: Shah owns shares in and serves on 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).