Scientists are taking advantage of a new way to turn cancer cells into powerful anticancer agents. Khalid Shah’s team, from Brigham and Women’s Hospital (USA), has developed a new cell therapy approach that is capable of simultaneously eliminating tumors and inducing long-term immunity, training the immune system to prevent the recurrence of cancer.
The researchers have already tested their dual-acting cancer vaccine in an advanced mouse model of glioblastoma, a deadly brain cancer, with promising results. The results are published in “Science Translational Medicine.”
“Our team has pursued a simple idea: take cancer cells and turn them into vaccines and cancer killers,” Shah says. “Through genetic 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.”
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 reuses live tumor cells, which have an unusual characteristic. Like homing pigeons, living tumor cells travel long distances through the brain to return to where their mates are.
Taking advantage of this unique property, Shah’s team manipulated living tumor cells using the CRISPR-Cas9 gene-editing tool and repurposed them to deliver a tumor cell-killing agent. In addition, the modified tumor cells were engineered to express factors that make it easier for the immune system to detect, label, and memorize them, preparing the immune system for a long-term antitumor response.
This dual-action cell therapy was found to be safe, applicable, and effective in these models, suggesting a roadmap toward therapy.
The team tested their CRISPR-enhanced and reverse-engineered therapeutic tumor cells (ThTC) in different strains of mice, including one containing human-derived bone marrow, liver and thymus cells, mimicking the human immune microenvironment.
In addition, a two-layer kill switch was embedded in the cancer cell that, when activated, eradicates ThTC if necessary.
This dual action cell therapy resulted safe, applicable and effectivez in these models, suggesting a road map to therapy.
Although further testing and development is needed, Shah’s team specifically chose this model and used human cells to pave the path of transferring their findings to patients.
Shah and colleagues note that this therapeutic approach is applicable to a broader range of solid tumors and that further investigation into its applications is warranted.