Scientists create vaccine to kill, prevent brain cancer cells - study

Cancer vaccines are an active area of research for many labs, but the approach that Shah and his colleagues have taken is unique.

 Cancer Immunotherapy by  NIH Image Gallery. (photo credit: FLICKR)
Cancer Immunotherapy by NIH Image Gallery.
(photo credit: FLICKR)

Cancer cells are scary and an enemy to good health, but US researchers have found a way to make them friendly as potent, anti-cancer agents. In the latest study on lab rodents by Dr. Khalid Shah at Brigham and Women’s Hospital in Massachusetts, the investigators have developed a new cell therapy approach, creating a vaccine to eliminate established tumors and induce 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 brain cancer glioblastoma, with promising results. Findings have just been published in Science Translational Medicine under the title “Bifunctional cancer cell-based vaccine concomitantly drives direct tumor killing and antitumor immunity.”

“Our team has pursued a simple idea – to take cancer cells and transform them into cancer killers and vaccines,” said Shah, director of the Center for Stem Cell and Translational Immunotherapy and the vice chairman of research in the neurosurgery department at the Brigham and faculty at Harvard Medical School and the Harvard Stem Cell Institute. “Using gene 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 that Shah and his colleagues have taken is unique. Instead of using inactivated tumor cells, the team repurposes living tumor cells that possess an unusual feature – like homing pigeons returning to roost, living tumor cells will travel long distances across the brain to return to the site of their fellow tumor cells. 

How did the team conduct its research?

Taking advantage of this unique property, Shah’s team engineered living tumor cells using the gene-editing tool CRISPR-Cas9 and repurposed them to release tumor-cell killing agents. The engineered tumor cells were also designed to express factors that would make them easy for the immune system to spot, tag and remember, thus priming the immune system for a long-term anti-tumor response.

Two genetically engineered T Cells (light green) attacking a cancer cell in red. (credit: TILDA BARLIYA/ASTAR SHAMUL/CYRILLE COHEN)Two genetically engineered T Cells (light green) attacking a cancer cell in red. (credit: TILDA BARLIYA/ASTAR SHAMUL/CYRILLE COHEN)

The team tested their repurposed CRISPR-enhanced and reverse-engineered therapeutic tumor cells (ThTC) in different mice strains including the one that bore bone marrow, liver and thymus cells derived from humans, mimicking the human immune microenvironment.

The team also built a two-layered safety switch into the cancer cell, which, when activated, eradicates ThTCs if necessary. This dual-action cell therapy was safe, applicable and efficient in the animal models, suggesting a roadmap toward therapy.

While further testing and development are needed, Shah’s team specifically chose this model and used human cells to smooth the path of translating their findings for patient settings.

“Throughout all of the work that we do in the center, even when it is highly technical, we never lose sight of the patient,” concluded Shah.

“Our goal is to take an innovative but translatable approach so that we can develop a therapeutic, cancer-killing vaccine that ultimately will have a lasting impact in medicine.”

Dr. Khalid Shah

The team said that their therapeutic strategy is applicable to a wider range of solid tumors and that further investigations of its applications are warranted.