A team of scientists is trying to make cancer its own enemy. Their experimental vaccine candidates use modified tumor cells to deliver a toxic drug to cancer cells, while making it easier for the immune system to target and remember cancer. In new research, the vaccine has shown promising results against the most common form of brain cancer in experiments in mice.
Cancer vaccines are usually therapeutic, meaning they are aimed at treating existing cancers or preventing their recurrence. They try to take advantage of a feature in the cancer’s armor that normally allows it to escape the immune system. They train immune cells to recognize some important parts of cancer cells, such as cancer-specific proteins, using inactivated cancer cells or another delivery method (including viruses).
But the team led by Khalid Shah of Harvard Medical School and Brigham and Women’s Hospital is working on a slightly different approach. Their plan is to take live cancer cells and genetically transform them into “traitors.”
“Our team pursued a simple idea: we take cancer cells and turn them into cancer killers and vaccines,” says Shah, director of the Center for Stem Cell and Translational Immunotherapy at Harvard and Brigham.
By keeping cancer cells alive, the team hopes to capitalize on their natural propensity to search for their own kind. But these engineered therapeutic tumor cells, or ThTCs as the researchers invented, are modified in two important ways using CRISPR-Cas9. First, it aims to make cells produce potent tumor-killing agents. Second, they want to produce other proteins that will attract the attention of the immune system, and ideally, allow the body to naturally build long-term immunity against cancer. To further ensure the safety of the treatment, the cells are programmed to carry a double kill switch that would allow them to be easily destroyed if they try to continue to spread.
In the study, published in Science Translational Medicine, the team used the vaccine against glioblastoma tumors, the most common and often fatal type of brain cancer. Among different mouse strains, including mice bred to have human-like immune systems, the vaccine appeared to be safe and effective at killing tumors, triggering a sustained immune response, and prolonging mouse survival.
Scientists say clinical trials of the vaccine will begin in three to five years.
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