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August 10, 2022

An unexpected ally in cancer treatment

Aaron LeBeau, associate professor in the Department of Pathology and Laboratory Medicine at the University of Wisconsin-Madison, feeds nurse sharks pieces of squid in his research lab on December 15, 2021. LeBeau has discovered antibodies from sharks that can neutralize Covid-19 and related coronaviruses. While they won't be a treatment for the current pandemic, they can help prepare for the coronaviruses of the future that have yet to jump to people. (Photo by Bryce Richter / UW-Madison)

It seems unusual to think of sharks coming to a person’s rescue.

But the research underway by Dr. Aaron LeBeau, associate professor in the Departments of Pathology and Lab Medicine and Radiology, examines the use of shark antibodies, as well as those derived from camelids, for new targeted imaging and therapeutic agents for metastatic prostate cancer.

“We basically harness the power of the immune system and engineer it to attack cancer cells—to target proteins specific to the surface of cancer cells,” LeBeau said.

LeBeau’s team specializes in a technique called antibody phage display, where they can evaluate different types of antibodies through the use of a bacteriophage—a virus that infects bacteria. Their work involves developing their own large libraries of antibodies from sharks as well as camelids, which include llamas and camels.

These animals have antibodies that are smaller and more flexible than human antibodies, LeBeau said.

“So what we do is we rip out the immune system from various organisms and then display their antibodies on the surface of bacteriophage,” LeBeau said. “We developed these huge antibody libraries to screen for antibodies specific for our cancer target of interest that day.”

Once his team determines the most promising antibodies, they attach an imaging isotope to test its imaging potential. They can also swap that imaging isotope for a radiotherapy isotope to deliver targeted treatment.

“So we get a clear picture of where all the cancer cells are, how many are there, and then we try to weaponize our antibodies to eliminate it. Like little cancer hunters,” LeBeau said.

This research is currently being done in mice, though LeBeau hopes to expand to human trials in five to 10 years. LeBeau’s research has been funded by the Andy North and Friends initiative, as well as UW Carbone’s Innovation Fund.

Right now, there are limited treatment options for metastatic prostate cancer. Currently, the protein prostate-specific membrane antigen (PSMA) can be targeted using isotope labeled small molecules for both positron emission tomography imaging as well as radiotherapy for these patients.

“The problem is, as the disease progresses, as patients undergo different courses of therapy, the prostate cancer stops making PSMA and develops this new sort of look on the cell surface that is PSMA negative,” LeBeau said. “So we need to find markers, new agents against that subset of prostate cancer that is PSMA negative. That’s our work.”

The development of better imaging tools for late-stage prostate cancer not only helps guide more effective targeted treatments but also helps oncologists monitor the disease progression and if a therapy is working. Effective imaging is also crucial to help researchers who are developing new treatments.

“Being able to image the cancer accurately directly affects the approval of new therapeutic drugs,” LeBeau said. “You want to make sure your new drug works, but the problem is you can’t always image the cancer. So you have this crazy paradox where, we need new drugs but we have to figure out if they’re actually working. But we can’t tell if they’re working without good imaging.”