Cancer; Discovery; ENT

Fluorescent nanoprobe lights the way to reducing spread of cancer cells

Cancer; Discovery; ENT

Baran Sumer, M.D. (left), and Jinming Gao, Ph.D., have developed a fluorescent nanoprobe that lights up tumors for removal. Their discovery has earned a Breakthrough Therapy Designation from the FDA.

For patients with tumors in the lining of the abdominal wall, the prospect that some cancer cells could go unnoticed during surgery is very real. Despite advances in imaging and removal techniques, peritoneal cancer cells are notoriously proficient at evading detection, increasing the risk of recurrence and the need for additional surgery.

But a “breakthrough” therapy discovered at UT Southwestern and fast-tracked by the U.S. Food and Drug Administration (FDA) is making it possible for surgical oncologists to highlight and excise additional cancerous tissue at 50%-60% higher rates.

Dubbed the fluorescent nanoprobe, the real-time surgical imaging agent (licensed by OncoNano Medicine, Inc.), uses novel pH-sensitive nanotechnology to detect acidity and make the edges of solid metastatic tumors glow during cancer surgery while normal cells remain dark.

The enhanced visibility allows surgeons to remove more cancer cells throughout the abdomen that can’t be seen with standard imaging technology, spotlighting tumors as small as a half-millimeter in diameter – thinner than a pencil lead. The result is more complete tumor removal and reduced risk of cancer recurrence.

The fluorescent nanoprobe is just the third imaging agent to receive the FDA’s Breakthrough Therapy Designation, which accelerates the development and review process for in-demand, effective drugs. Early data from our Phase 2 clinical trial show that the nanoprobe identifies 10 times more metastatic cancer cells than the FDA’s minimum 5% threshold for successful detection.

“We saw that in animal models, we could detect cancers down to a half-millimeter," says Baran Sumer, M.D., We didn’t expect that level of specificity in human samples, but that’s what we got! It was a very, very nice surprise.”

How the nanoprobe works

Healthy cells “eat” glucose, or sugar, to gain energy, divide, and heal themselves. Cancer cells, by comparison, consume glucose at a much higher volume to change their makeup, grow, and spread. The resulting byproduct is a tumor that secretes high levels of lactic acid, crippling the immune system’s defenses against the cancer.

The fluorescent nanoprobe uses novel pH-sensitive nanotechnology to detect acidity and make the edges of solid metastatic tumors glow during cancer surgery.

Called the Warburg effect, this process occurs in all types of cancer and it is the target that our nanoprobe uses to identify residual metastatic tumors in the peritoneum – the thin layer of cells that line the abdominal wall and cover the uterus, bladder, stomach, intestines, and rectum.

The nanoprobe is delivered through an IV about 24 hours before surgery. As the imaging agent pegsitacianine circulates through the body, it “digitizes” the acidic signals from cancer cells. The nanoprobe is switched “off” while circulating in normal pH and turns “on” when the sensors detect acidity.

When switched “on,” dissociated cationic polymers attach to the cancer cells, lighting them up under near-infrared light. Using an intraoperative camera, the surgeon can better visualize the glowing cells and remove them with extreme precision.

We designed pegsitacianine to light up quickly in an acidic environment and also to be compatible with the cameras integrated into surgical suites, including the da Vinci robot system.

Expanding cancer targets in the future

Because the nanoprobe technology targets the Warburg Effect, it is tumor-agnostic and could potentially be used in other forms of cancer, starting with head and neck cancer – a common area of the body for metastatic cells to spread.

Besides peritoneal metastasis, the National Cancer Institute has awarded UT Southwestern a clinical R01 grant to study the use of the nanoprobe to locate unknown primary cancer in the head and neck. That trial is scheduled to open in late summer 2023.

OncoNano Medicine, Inc., has also received a Small Business Innovation Research (SBIR) grant to further develop the technology and conduct a Phase 3 clinical trial for metastatic peritoneal tumors. Once it earns FDA approval, the trial will be held at multiple U.S. centers, including UTSW.

Next up for the nanoprobe are two adaptations of the technology being tested in human studies:

  • A “nanovaccine,” in which we are working to train the immune system to produce tumor-specific T cells to target the adaptor protein STING (stimulator of interferon genes) to initiate an immune response against the cancer.
  • Reversing the Warburg effect to neutralize the acidic tumor environment and keep the immune system functional to eliminate cancer cells.

We also anticipate physicians will explore diagnostic uses for this intraoperative technology, which could inform surgical decisions and strategies in real time.

At UT Southwestern, we are continuing to push forward with research and creating clinical applications for the nanoprobe – all in pursuit of saving lives and reducing the burden of metastatic cancer.

To discuss your options for peritoneal cancer treatment, call 214-645-8300 or request an appointment online.

Drs. Gao and Sumer each have financial interests in OncoNano Medicine, Inc., as does UT Southwestern.

Illuminating Cancer Surgery

Baran Sumer, M.D., joins UT Southwestern's web series Science Café to explain the mechanisms behind his leading-edge cancer tumor research. Together with scientist Jinming Gao, Ph.D., he has developed a breakthrough therapy that targets tumors, light up their margins, and makes possible more accurate surgery and treatment.