Harvard University: Treating cancer with cancer

Scientists develop cell therapies to kill and prevent brain cancer in advanced mouse models

Scientists at Brigham and Women's Hospital are using a new method to turn cancer cells into effective anti-cancer drugs
.

Researchers from Khalid Shah's lab, Harvard-affiliated BWH, have developed a new cellular therapy approach that eliminates established tumors and induces long-term immunity, training the immune system so that it can prevent cancer recurrence
.
The team tested their dual-acting anti-cancer vaccine in an advanced mouse model of the deadly brain cancer glioblastoma, and the results were promising
.
The findings were published in the journal Science Translational Medicine
.

"Our team has been pursuing a simple idea: take cancer cells and turn them into cancer killers and vaccines," said corresponding author Khalid Shah, director of the Center for Stem Cell and Translational Immunotherapy, associate director of Brigham Neurosurgery Research, and faculty
member at Harvard Medical School and Harvard Stem Cell Institute.
Through genetic engineering, we are repurposing cancer cells to develop a treatment that kills tumor cells and stimulates the immune system to destroy the primary tumor and prevent cancer
.
”

Cancer vaccines are an active area of research in many labs, but the approach taken by Shah and his colleagues is unique
.
Instead of using inactivated tumor cells, the team repurposed live tumor cells
with unusual characteristics.
Just as carrier pigeons return to their habitat, live tumor cells travel long distances in the brain back to their tumor cell companions
.
Using this unique property, Shah's team used the gene-editing tool CRISPR-Cas9 to engineer living tumor cells and repurpose them to release tumor cell killers
.
In addition, engineered tumor cells are engineered to express factors that make them easily discoverable, labeled, and remembered by the immune system, preparing them for a long-term anti-tumor response by the immune system
.

The team tested their repurposed CRISPR-enhanced and reverse-engineered therapeutic tumor cells (ThTCs) in different mouse strains, including bone marrow, liver, and thymus cells from humans, mimicking the human immune microenvironment
.
Shah's team also built a two-layer safety switch in cancer cells that, when activated, eradicated THTC
if needed.
This double-acting cell therapy is safe, applicable and effective in these models, providing a roadmap
for treatment.
While further testing and development is needed, Shah's team specifically chose this model and used human cells to pave the way
for translating their findings into patient settings.

"In all the work we do at our center, even highly technical work, we never neglect patients
," Shah said.
Our goal is to take an innovative but translatable approach so that we can develop a therapeutic anti-cancer vaccine that will ultimately have a lasting impact
on medicine.
Shah and colleagues note that this treatment strategy is applicable to a wider range of solid tumors and that further research
into its application is warranted.