COLUMBIA, Mo. — This year alone, the American Cancer Society estimates almost two million new cancer cases will occur in the United States, and at least 25% of cases may be fatal. That’s why Paul de Figueiredo and his team at the University of Missouri are working to lower these numbers through the Synthetic Programmable bacteria for Immune-directed Killing in tumor Environments (SPIKEs) project. The goal of the project is to build an inexpensive and safe therapeutic using bacteria that can recruit and regulate tumor-targeting immune cells to help the body fight cancer cells without the side effects of traditional medications.
Supported by a $19 million Advanced Research Projects Agency for Health (ARPA-H) grant that is part of President Joe Biden’s Unity Agenda in support of Cancer Moonshot objectives, de Figueiredo’s project is designed to, ultimately, decrease cancer deaths and improve patients’ quality of life. This multifaceted research combines technological and biomedical advancements to develop a single-dose treatment that can stimulate cancer patients’ immune systems.
“Cancer kills, and there are some cancers for which there are no interventions,” said de Figueiredo, a Roy Blunt NextGEN Precision Health-endowed professor of molecular microbiology and immunology and Bond Life Science Center researcher. “But simultaneously, we also need to solve the cost problem. Many state-of-the-art interventions cost half a million dollars to implement per patient, which will not help anybody with limited resources. So, we are trying to develop a technology that can not only address cancers that can’t be attacked with current approaches, but also do it in a way that is far less costly.”
Many forms of cancer, including colon, pancreatic, and lung cancers, remain particularly difficult to treat with interventions that are often ineffective. However, cancer immunotherapies — treatments that harness the body’s own immune system to attack tumor cells — offer promise in this realm, de Figueiredo said.
Inspired by the potential of immunotherapy, de Figueiredo and his team will work to engineer a synthetic biological solution over the next 12 months to craft a safe bacterial therapeutic that can sense and respond to its environment. That includes an accompanying “kill switch,” which will tell the microbe to die if it enters a part of the body it shouldn’t.
“Developing a single-dose medicine to address cancer is a pretty hard problem,” de Figueiredo said. “One of the things that we think microbes are really good at — because they carry genetic material — is their ability to target multiple areas simultaneously. In addition, if a patient starts to have a bacterial-associated side effect, you can give the patient a bacteria-killing antibiotic to clear the microbe. If we can program the bacteria’s genetic circuit to be super sensitive to antibiotics, that would be helpful in this case.”
It’s important to note, however, that this bacterial therapeutic alone will not kill cancer cells, de Figueiredo said. What it will do is activate the body’s immune response — essentially awakening dormant immune cells that are affected by the cancerous tumor and let those cells fight the pathogen naturally.
“Most interventions today are akin to a single rifle shot, such as taking one drug that attacks one target,” de Figueiredo said. “This approach can work and people can get better. But the conceptual space we’re trying to access in our project is more of a shotgun approach, where we seek to obliterate multiple targets because of the bacterial therapeutic’s multi-faceted targeting system.”
Using CRISPR technology, which is used for genetic engineering, the research team will exploit recombinant molecular biology to reengineer the microbe to have this new, life-saving potential. In terms of affordability, de Figueiredo outlined three factors that would keep the cost down:
- The manufacturing is scalable. For example, similar strategies used to grow the microbes that make beer could also be used to make these microbes.
- Microbes have the potential to be delivered absent a cold supply chain. This means the therapeutic would be able to be delivered to remote locations without the obstacle of needing refrigeration.
- Bacterial therapeutics could potentially have universal applications. With human cell treatments, the cells have to be compatible with the person receiving the treatment. Bacterial interventions don’t require the same match compatibility.
“I think we all have experience with cancer on some level, and while that is part of my story, the truth is that I want to do something impactful,” de Figueiredo said. “This research is the vehicle that allows me to do that and make meaningful changes in people’s lives.”