JUL 22, 2017 08:24 AM PDT

Scientists Train Immune Cells to Gobble Up Cancer


Cancer cells evolved to have cunning strategies to protect themselves against the body’s defenses. One of these strategies involve expressing the “don’t eat me tag” so as to fool immune cells into treating it as healthy cells. But now, scientists have wised up to cancer’s tricks and have re-engineered immune cells to recognize and attack these disguised cancer cells.

Image credit: Pixabay.com

The body is equipped with immune cells that recognize and attack cells that it perceives as foreign invaders. Macrophages are among these fighter cells. Considered the “first responders,” these cells gobble up diseased and foreign bodies to protect the body. Its name derives from the Greek for “big eater.”

Healthy cells protect themselves from the macrophage’s destruction by expressing CD47, a surface protein that serves as a “marker of self.” But because cancer cells are mutated versions of healthy cells, they also express CD47. Thus, instead of attacking cancer cells, macrophages let these invaders go untouched because they’ve been tricked into thinking these cells are part of the normal system.

Knowing this trickery, scientists at the University of Pennsylvania sought to help macrophages better distinguish between healthy and cancerous cells. They did this by blocking the interaction of CD47 to surface proteins on the macrophages, known as SIRPA.

"Our new approach takes young and aggressive macrophages from the bone marrow of a human donor and removes a key safeguard that cancer cells have co-opted to prevent them from being engulfed," said Cory Alvey, the study’s lead author.

But there was a problem. While modified macrophages would recognize cancer cells as foreign and launched attacks on these, it also attacked healthy cells in a similar fashion. Indeed, previous studies in mice showed that blocking the interaction between CD47 and SIRPA did decrease cancer cells. But the mice also lost healthy blood cells, became anemic, and some even died.

To solve this problem, the team introduced antibodies that were specific to cancer cells. These would allow macrophages to zero in on the cancer cells that are now unmasked and targeted.

"Combined with cancer-specific targeting antibodies, these engineered macrophages swarm into solid tumors and rapidly drive regression of human tumors without any measurable toxicity,” said Alvey.

The team showed that with just two injections, dime-sized tumors shrank by 80 percent. Furthermore, the cancer cell count decreased by 100-fold. "The big surprise," said Dennis Discher, "is that injected macrophages circulate all around the body but accumulate only within the tumors where they engorge on cancer cells." Discher is a professor in Penn Engineering's Department of Chemical and Bimolecular Engineering, and the study’s senior author.

"Safety thus far is likely a consequence of both the relatively small number of engineered macrophages that are injected and their sequestration into the tumors, away from most healthy cells," Discher said.

“The first phase of clinical trials are tests of human safety, so this is a promising start," Alvey said. "The potency of these engineered macrophages is relatively clear, but the crucial issue is how to maximize the anticancer effects while minimizing side effects, namely the engulfment of normal cells." In addition, the team is working to make the anticancer effects longer-lasting.

Additional sources: University of Pennsylvania


About the Author
  • I am a human geneticist, passionate about telling stories to make science more engaging and approachable. Find more of my writing at the Hopkins BioMedical Odyssey blog and at TheGeneTwist.com.
You May Also Like
JUN 05, 2018
Cell & Molecular Biology
JUN 05, 2018
Mechanism of Aspirin's Anti-Colon Cancer Effects Revealed
For some people, aspirin can help prevent colon cancer; now researchers have learned more about how that happens....
JUN 07, 2018
Clinical & Molecular DX
JUN 07, 2018
Digital Screening Vital for Detecting Breast Cancer
A combination of two digital techniques could be the best way to diagnose breast cancer. In a new study, scientists show how combining a technique called t...
JUL 24, 2018
JUL 24, 2018
Transfection, Transduction, and CRISPR...Oh My
CRISPR gene editing came about based on transfection and transduction type models of genetic transfer. There is potential for it to revolutionize gene editing but are there dangers lurking?...
JUL 25, 2018
JUL 25, 2018
Can CT Scans Increase the Risk of Brain Cancer?
Medical imaging has gone from fuzzy X-rays that didn't show much, to real-time functional MRI scans in just a few decades. Being able to see inside the...
AUG 14, 2018
AUG 14, 2018
Can Zika Virus Help Neuroblastoma Patients?
Researchers in Florida published the potential for Zika virus to help in the treatment of Neuroblastoma in patients of all ages....
OCT 06, 2018
Drug Discovery
OCT 06, 2018
New Class of Drugs for Breast Cancer Therapy
Scientists at Stevens Institute of Technology have designed a new class of molecules that may hold the potential to add to the arsenal of drugs actively be...
Loading Comments...