Solid tumor cells carry a “don’t eat me” signal to escape attacks by the immune system. Disrupting this tumor-protecting signal could mean developing a single drug that can fight at least 7 different types of cancer, a new study shows.
Tumor cells from a range of cancer types all express a protein called CD47 – the “don’t eat me” sign that prevents tumors from being chewed up by immune cells.
Solid tumors grow unchecked and metastasize to other sites by evading phagocytosis, the process of being engulfed and digested by immune cells. Years ago, Stanford scientists showed that drugs that block CD47 can eliminate tumors in mice with leukemia and lymphoma.
"What we've shown is that CD47 isn't just important on leukemias and lymphomas," says the new study’s lead author, Irving Weissman from Stanford. "It's on every single human primary tumor that we tested."
In particular, they looked at: ovarian, breast, colon, bladder, glioblastoma (brain), hepatocellular carcinoma (liver), and prostate tumor cells.
They exposed tumor cells to immune cells called macrophages and anti-CD47 molecules in a petri dish. They also transplanted human tumors into the feet of mice, and when they treated the mice with anti-CD47, the tumors shrank and didn’t spread to the rest of the body:
- Only one of 10 mice treated with anti-CD47 had a lymph node with signs of cancer.
- Colon cancers transplanted into the mice shrank to less than one-third of their original size on average.
- In 5 mice with breast cancer tumors, anti-CD47 eliminated all signs of the cancer cells, and the animals remained cancer-free 4 months after the treatment stopped.
"We showed that even after the tumor has taken hold, the antibody can either cure the tumor or slow its growth and prevent metastasis," Weissman says.
They also found that, while many normal cells in the body also have CD47 to avoid being destroyed, cancer cells have higher levels of CD47 than healthy cells. How much CD47 a tumor made could predict the survival odds of a patient.
Weissman's team has received a $20 million grant from the California Institute for Regenerative Medicine to move the findings from mouse studies to human safety tests.
A 2010 Weissman study showed that cancer cells also carried an “eat me” sign on them.
The new study was published in the Proceedings of the National Academy of Sciences this week.
Image: CD47 via Wikimedia