Texas A&M University researchers co-lead a $20 million project to develop a $1 cancer treatment. With support from federal funds, a multi-university team of researchers is developing a highly effective bacterial therapy that more precisely targets cancer with a single, $1,000 dose, making treatment safer.

Traditional cancer therapies have limited effectiveness in treating patients. Some treatments, such as radiation and chemotherapy, can have harmful side effects, while others often leave patients unresponsive, not to mention the expense of receiving treatment. Survey results from the American Cancer Society Cancer Action Network show that 73% of cancer survivors and patients are worried about how to pay for cancer treatment, and 51% report incurring medical debt due to treatment. For example, state-of-the-art cancer treatments can cost up to $1 million.

Texas A&M University and the University of Missouri are leading the effort to develop a low-cost, safe, and controllable cancer treatment. The researchers received a $20 million anti-cancer grant from the Advanced Research Projects Agency for Health (ARPA-H). The four-year project is part of this government's Cancer Month initiative to promote and increase funding for cancer research. This is one of the first projects funded by the newly formed agency, which aims to accelerate improvements in health for everyone by supporting the development of high-impact solutions to society's most challenging health problems.

Quickly analyze cells

Texas A&M Engineering Experiment Station/Texas A&M University co-principal investigators Arum Han, Ph.D., Jim Song, Ph.D., and Chelsea Hu, Ph.D., are developing synthetic programmable bacteria (SPIKEs) for immune-directed killing in the tumor environment. The idea is to have the bacteria help T cells kill cancerous tissue, and once the cancer cells are gone, the bacteria will self-destruct and safely leave the body as body waste.

"SPIKEs can specifically target tumor cells," said Han, a professor in the Department of Electrical and Computer Engineering at Texas Instruments. "Because it targets only cancerous tissue and not surrounding healthy cells, patient safety is increased exponentially. It's an honor to join this team and solve a major health problem that affects so many people."

Han's lab is developing high-throughput microfluidic systems that can rapidly process and screen large libraries of bacterial therapeutics, one cell at a time, to quickly identify the most promising treatments. By integrating microfabrication methods and biotechnology, these systems enable picoliter-capacity liquid handling systems that can accurately analyze single cells with high accuracy and speed, creating devices for rapid analysis of single cells.

"The main challenge is how to actually develop these sophisticated microdevices that allow us to perform millions of fully automated tests with little to no manual or human intervention," Han said. "That's the engineering challenge."

Rescue anti-tumor immune cells

While Han was innovating and designing tiny devices, Song, an immunologist with a background in microbial pathogenesis, T cell biology, and T cell-based immunotherapy, has been working on bacterial immunotherapy for the past five years. A bacterium called Brucella melitensis can manipulate the human body's microenvironment to promote T cell-mediated anti-tumor immunity, thereby treating at least four types of cancer.

Song, a professor at the Texas A&M University School of Medicine, said: "We are working hard to improve Brucella to more effectively prevent or inhibit tumor growth. The current approach is to find out how to engineer the bacteria to rescue anti-tumor immune cells and increase their efficiency in killing tumor cells. The data so far show that Brucella is much more efficient than other cancer therapies such as chimeric antigen receptor T-cell therapy and T-cell receptor therapy, with a response rate of more than 70%."

While Song continues to test the bacteria's efficiency using cancer models, Hu, a synthetic biologist and assistant professor in the Atty-McFerrin Department of Chemical Engineering, is working to ensure that live bacterial therapies are safe and controllable.

"The Brucella strain we used has been shown to be safe for the host because it is an attenuated version, meaning a key gene required for the bacteria's virulence has been deleted," Hu said. "Ultimately, we hope to control how quickly the bacterium grows, where it grows within the tumor environment and its ability to self-destruct after completing its mission."

To control the rate of growth, the bacteria's genes will be altered to regulate their numbers and swing around a specific set point. Hu also plans to add biosensors to the bacteria to enable the bacteria to distinguish between healthy tissue and tumor tissue, ensuring that bacteria only grow in the tumor microenvironment.

The bacteria will be engineered to have a receptor that ensures that once the cancer is gone, the patient can be given an antibiotic that will signal the bacteria to essentially cut itself into pieces and be safely removed from the patient's body.

"As humans, our bodies are literally covered in bacteria, and many diseases are caused by imbalances in these bacterial communities," Hu said. "For example, some people have very fragile stomachs, while others have strong stomachs. The science behind this is that people with strong immune and digestive systems have healthy communities of bacterial cells in their guts. In vivo therapies have great potential."

"It's a really great opportunity to have a great team that has the expertise and the ability to push this technology to the forefront," Hu said. "So our goal is to move into the clinic and provide patients with an effective cancer treatment that costs less than $1 per dose."

Use unconventional methods to solve difficult problems

Other collaborators include Dr. Zhilei Chen of the Texas A&M University Health Science Center, Dr. Xiaoning Qian of the Department of Electrical and Computer Engineering, and principal investigator Dr. Paul DeFigueredo of the University of Missouri.

"The three main advantages of this work are high safety, low cost and specific targeting of cancer tumors," Han said. "We are excited to be one of the first teams to receive support from ARPA-H, a brand new agency established and supported by the U.S. Congress to truly solve difficult problems in a wide range of health areas. We are solving difficult problems with unconventional methods. High risk, high impact are the hallmarks of our approach."

The future applications of engineered bacteria opened up by this research are limitless.

"In our next big project, we will collaborate to engineer bacteria to fight autoimmune diseases such as type 1 diabetes and rheumatoid arthritis," said Song. "Bacteria-based immunotherapy is a breakthrough frontier in medicine and has the potential to revolutionize the treatment of autoimmune diseases. Harnessing the power of beneficial microbes to modulate the immune system, we are on the verge of changing the future of medicine. Our research and expertise are expected to transform the lives of millions of people, giving them new hope and a healthier tomorrow."

Compiled source: ScitechDaily