Quanyin Hu, an assistant professor in the University of Wisconsin-Madison’s School of Pharmacy, aims to develop personalized vaccines that prevent post-surgical recurrence of aggressive tumors. Using their vaccines, Hu and his research team successfully slowed recurring tumor growths in mice.
A prominent concern in cancer treatment is that a tumor might return after an initial surgery to remove it. The recurrence rate can be particularly high in aggressive cancers such as certain breast cancers and melanoma.
An unexpected finding
Hu and his team focus on improving the long-term prognosis of cancers by reducing their tendency to reoccur after treatment.
Recently, Hu’s lab found a way to make vaccines induce cell pyroptosis, a type of inflammatory cell death that triggers an immune response. This helps the body recognize and attack cancer cells, preventing recurrence long-term.
Current tumor vaccines are limited in their ability to address individual differences in tumor antigens, proteins found on the surfaces of cancer cells that help the immune system recognize and respond to cancer cells. Individual and tumor-specific differences in tumor antigens are important to address to develop personalized cancer treatments.
Hu’s vaccines would be able to trigger each patient's unique “immunogenic cancer cell base,” which includes specific tumor debris and signals that remain after cancer cells undergo pyroptosis. The immunogenic cancer cell base primes the immune system to respond to cancer later on.
“We were looking at ways to trigger the cancer cell pyroptosis because we found that this cancer cell pyroptosis can induce the immunogenic cancer cell base,” Hu told The Daily Cardinal.
Hu’s team noticed that dying cancer cells were releasing large amounts of particles that did not match what had been previously described in the literature. Upon further investigation, Hu and his team confirmed that they had identified a new type of vesicles called pryoptic vesicles.
“When we looked at the morphology of the cancer cell undergoing pyroptosis, we found these cells were secreting a lot of extracellular vesicles… we suspected this was not the classic tumor exosomes,” Hu said.
These pryopic vesicles contain tumor specific antigens and molecular bits that can suppress cancer after tumor removal and activate the immune system against cancer. These features make the vesicles ideal candidates for personalized cancer vaccines, since the vesicles are derived directly from the patient's tumor and allow the vaccine to be tailored to the individual.
To test out the effectiveness of the vesicles in preventing recurrence after surgery, the vesicles were paired with an immune stimulant to boost the immune response to any cancer cells. The vesicles were then inserted into a biocompatible hyaluronic acid hydrogel, forming a substance called PyoVAC. The hydrogel allowed the vesicles to be released safely into the body over time.
PyoVAC was implemented in three types of cancer-infected mice: mice with melanoma, triple negative breast cancer and a humanized breast cancer model from patient tumor samples.
Hu said he chose these models because of the clinical need to prevent recurrence in cancers that frequently return.
“Triple-negative breast cancer and melanoma have very high chances of coming back after surgery,” Hu said. ”Our goal is to fill this unmet clinical need by preventing post-surgical recurrence.”
At this point, the mouse studies have shown promise.
Hu said five or six out of eight mice became tumor-free in one study, proving the vaccine was able to “completely eradicate” post-surgical tumor recurrence. “That piece of data really got me excited, because it reflects the huge potential of this vesicle-based vaccine,” he said.
Hu sees these results as promising for improving the prognosis of several types of cancers.
“We really want to translate these technologies [to humans],” Hu said. “We want to examine the toxicity of these vesicles and establish protocol for the future. There is still a long way to go before we can implement this clinically, but we see the translational potential.”
