On October 6th, the very day the 2025 Nobel Prize in Physiology or Medicine was awarded for groundbreaking work in T-cell based cancer immunotherapy, We had the pleasure of hosting a talk that perfectly echoed this theme of immune innovation. We welcomed Dr. Iva Hafner Bratkovič, a research professor at the Department of Synthetic Biology and Immunology in Slovenia’s National Institute of Chemistry, for our CTGCT Science Talks webinar series. Her presentation, “Inflammasome-inspired cancer immunotherapy”, presented a fascinating and innovative strategy: turning the body’s own inflammatory machinery into a powerful tool against cancer.
Dr. Iva Hafner Bratkovič is a leading voice in the field of innate immunity, with a distinguished career that includes a Fulbright research scholarship at Boston Children’s Hospital / Harvard Medical School. Her group’s research focuses on the intricate mechanisms of inflammasome activation and the regulation of a specific form of cell death known as pyroptosis.
What are Inflammasomes? The Cell’s Internal Alarm System
To understand Dr. Hafner Bratkovič’s work, we first have to look at how our bodies detect “danger.” Our cells are equipped with molecular machines called inflammasomes. Think of these as a multi-part alarm system:
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The Sensor: A protein (like NLRP3) that stays “off” until it detects a threat. Like a virus, bacteria, or even signs of cellular stress.
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The Adapter (ASC): Once the sensor is triggered, it recruits an adapter protein called ASC. These proteins stick together to form a massive structure known as an “ASC speck.”
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The Effector (Caspase-1): This speck then activates an enzyme called Caspase-1.
Once active, Caspase-1 acts like molecular scissors. It cuts and activates inflammatory messengers called cytokines (specifically IL-1β and IL-18), which act as chemical “flares” to signal the immune system that help is needed.
But inflammasomes do more than just send signals. Caspase-1 also cuts a protein called Gasdermin D. The fragments of this protein travel to the cell’s outer membrane and punch holes in it.
This leads to a form of cell death called pyroptosis. Unlike apoptosis, where the cell is neatly recycled, a cell undergoing pyroptosis swells and bursts. It spills its contents, creating a localized “inflammation storm” that is difficult for the immune system to ignore.
Turning “Cold” Tumors “Hot”
The major hurdle in treating cancer is that many tumors are “cold.” This means they have found ways to hide from the immune system.
Dr. Hafner Bratkovič’s team uses synthetic biology to bypass the tumor’s camouflage. They deliver the “blueprints” (in the form of DNA plasmids) directly into the tumor to force the cancer cells to build these inflammasome machines.
By triggering pyroptosis inside the tumor, they turn a “cold” tumor into a “hot” one. The death of the cancer cell releases signals that draw in elite immune cells, such as NK (Natural Killer) cells and cytotoxic T cells, to finish the job.
As we celebrate the advancements in immunotherapy highlighted by the 2025 Nobel Prize, Dr. Hafner Bratkovič’s work serves as a reminder that we are only at the beginning of what is possible. By “rewiring” the very mechanisms that cause inflammation, the researchers at the National Institute of Chemistry and the CTGCT project are turning biological “threats” into life-saving treatments.
We are incredibly grateful to Dr. Hafner Bratkovič for sharing her expertise and look forward to the next steps in this fight against cancer!