In a major breakthrough, scientists at the Indiana University School of Medicine have found a way to transform immune cells that normally protect cancer into powerful tumor fighters.
The new research, published in Science Immunology, could lead to improved treatments for hard-to-treat cancers such as triple-negative breast cancer, colorectal cancer, and melanoma.
The immune cells at the center of this discovery are called regulatory T cells, or Tregs.
These white blood cells usually play a vital role in keeping the immune system under control, preventing it from attacking healthy tissues and causing autoimmune diseases.
However, inside tumors, these same cells become problematic—they protect cancer by blocking the body’s immune defenses from recognizing and destroying tumor cells.
“Regulatory T cells are essential for maintaining balance in the immune system, but eliminating them entirely would be dangerous,” explained Dr. Baohua Zhou, senior author of the study and professor of pediatrics and microbiology and immunology at Indiana University.
“Our goal was to change how these cells behave—so they attack tumors rather than defend them.”
To achieve this, the researchers focused on a gene called FOXP3, which governs how regulatory T cells develop and function.
Humans naturally make two forms of the FOXP3 protein—a long and a short version. The team designed a special molecule called a morpholino, which targets this gene and encourages cells to produce mostly the short version. This subtle shift completely changes the cells’ role.
“By switching which version of FOXP3 is made, our drug reprograms the T cells,” said Dr. Naresh Singh, co-first author of the study. “Instead of suppressing the immune system, they start helping other immune cells fight the cancer from within.”
The results were remarkable. In experiments with mice, those producing only the short version of FOXP3 completely eliminated aggressive triple-negative breast cancer tumors.
The new morpholino drug also worked effectively on human tumor samples from breast and colorectal cancer patients in the lab, suggesting the therapy could be broadly useful.
“Our preclinical tests showed incredible results in one of the deadliest forms of breast cancer,” Dr. Zhou said. “And the early data from other cancers look very encouraging too.”
The next step for the research team is to prepare clinical trials to test the safety and effectiveness of this approach in cancer patients. If successful, this method could mark the beginning of a new era in cancer immunotherapy—where the body’s own immune system is not only unleashed but reprogrammed to fight back smarter.
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