The impact of programmable bacteria on cancer treatment

https://www.eurekalert.org/news-releases/1009258

https://chat.openai.com/c/6cfb1180-0a40-409b-b230-817e653d2c44

Texas A&M University researchers are co-leading a $20 million project to develop a $1 cancer treatment.

What if a single dose of $1 could cure cancer?

A multi-university research team is receiving federal funding to develop a highly efficient bacterial therapy that targets cancer more precisely and makes treatment safer at a cost of $1 per dose.

Traditionally, cancer treatments have had limited effectiveness in treating patients. Some treatments, such as radiation therapy and chemotherapy, can cause harmful side effects, while others tend to have poor patient response, not to mention the high cost of treatment.Survey results from American Cancer Society Cancer Action Network reports that 73% of cancer survivors and patients are concerned about how they will pay for their cancer treatment, and 51% say they have medical debt from their treatment. For example, cutting-edge cancer treatment can cost up to $1,000,000.

Texas A&M University and the University of Missouri are leading efforts to develop low-cost, safe and controlled cancer treatments. Researchers received a $20 million grant from the Advanced Research Projects Agency for Health (ARPA-H) to fight cancer. The four-year project is part of the current administration’s cancer moonshot plan to boost cancer research and increase funding. It is funded by a newly established agency that aims to accelerate improved health outcomes for all by supporting the development of highly effective solutions to society’s most challenging health problems. It was one of my first projects.

Rapid analysis of cells

$12 million of the grant will go to the Texas A&M Engineering Experiment Station/Texas A&M. Alam Han, Jim Song, and Chelsea Hu are developing programmable synthetic bacteria for immune-induced killing in the tumor environment (SPIKE). The idea is to engineer the bacteria so that the T cells kill the cancerous tissue, and once the cancer is gone, they destroy themselves and are safely excreted out of the body as human waste.

“SPIKE can specifically target tumor cells,” said Han, a professor in Texas Instruments’ Department of Electrical and Computer Engineering. “And because we only target the cancerous tissue and not the surrounding healthy cells, patient safety is dramatically increased. I’m excited to be part of this team tackling a critical health issue that affects so many people. I am very honored.”

Han’s lab is developing high-throughput microfluidic systems that can rapidly process and screen large bacterial therapeutic libraries one cell at a time to rapidly identify the most promising treatments. By fusing microfabrication techniques and biotechnology, these systems create picoliter-scale liquid handling systems that can accurately analyze single cells with high precision and speed, and devices that rapidly analyze individual cells. Realize.

“The big challenge is figuring out how to actually develop these sophisticated microdevices that can run millions of fully automated tests with very little manual or human intervention,” Han said. said. “That’s the engineering challenge.”

Rescue anti-tumor immune cells

While Han innovates and designs microdevices, Song, an immunologist with a background in microbial pathogenesis, T-cell biology, and T-cell-based immunotherapy, has spent the past five years working in bacterial immunotherapy. We are working on this.certain bacteria known as Brucella melitensis At least four types of cancer can be treated by manipulating the human body’s microenvironment and promoting T cell-mediated antitumor immunity.

“We are working on improving Brucella melitensis We can more effectively prevent or suppress tumor growth,” said Song, a professor at Texas A&M School of Medicine. “Our current approach involves finding ways to manipulate bacteria to rescue anti-tumor immune cells and make them more effective at killing tumor cells.

“According to the data so far, BrucellaThe efficiency is dramatically higher than other cancer treatments such as chimeric antigen receptor T-cell therapy and T-cell receptor therapy, with a response rate of over 70%,” said Song.

Safe and controllable treatment

While Professor Song continues to test the effectiveness of bacteria using cancer models, Professor Hu, an assistant professor in Artie McFerrin’s Department of Chemical Engineering and a synthetic biologist, has demonstrated that live bacterial treatments are safe and controllable. We are working to confirm.

” Brucella The strain we are using is attenuated and has been shown to be safe for the host as it lacks key genes required for bacterial virulence,” Hu said. Told. “Ultimately, we want to control the rate at which bacteria multiply within the tumor environment and their ability to self-destruct when their mission is completed.”

To control the rate of growth, the bacteria’s genes are modified to regulate its population, which fluctuates around a certain set point. Hu also plans to incorporate biosensors into the bacteria, allowing them to distinguish between healthy and tumor tissue, allowing them to grow only within the tumor microenvironment.

The bacteria are engineered with receptors that allow patients to take antibiotics after the cancer has gone away. This sends a signal to the bacteria to essentially shred itself and safely remove it from the patient’s body.

“We humans are actually covered in bacteria, and many diseases are caused by imbalances in these bacterial communities,” Hu said. “For example, some people have incredibly fragile stomachs, while others have strong stomachs. The science behind this is that people with strong immune and digestive systems have a healthy gut. It means that it has a population of bacterial cells. There are many possibilities for biological therapy.”

“It’s a really great opportunity to have a great team with the expertise and the ability to push this technology to the forefront,” Hu said. “So the goal is to go into the clinic and provide patients with effective cancer treatment for less than $1 per treatment.”

Tackling difficult problems with unconventional approaches

Other collaborators include Dr. Zhilei Chen of Texas A&M Health Science Center, Dr. Xiaoning Qian of the Department of Electrical and Computer Engineering, and Principal Investigator Dr. Paul de Figueiredo of the University of Missouri.

“The three important advantages of this study are high safety, low cost, and specific targeting of cancerous tumors,” Han said. “We are very excited to be one of the first teams to receive support from ARPA-H, a brand new agency supported by Congress. We take an unconventional approach to tackling difficult problems. High risk, high impact is the hallmark of our approach.”

And the future applications of bacterial engineering that this research unlocks are limitless.

“For our next big project, we will work together to develop bacteria that fight autoimmune diseases such as type 1 diabetes and rheumatoid arthritis,” Song said. Bacteria-based immunotherapy is an exciting frontier in medicine and offers the potential to revolutionize the treatment of autoimmune diseases. With the power of beneficial microorganisms harnessed to modulate the immune system, we are changing the future of medicine. Our research and expertise promises to transform the lives of millions of people, giving them new hope and a healthier tomorrow. ”