Researchers develop $1 cancer treatment using engineered bacteria

What if a single dollar dose could cure cancer?

A multi-university team of researchers, supported by federal funding, is developing a highly efficient bacterial therapeutic to target cancer more precisely and make treatment safer via a single $1 dose.

Traditionally, cancer therapies have been limited in their effectiveness in treating patients. Some, such as radiation and chemotherapy, cause harmful side effects, while others tend to result in low patient responsiveness, not to mention the expense required to receive treatment. Findings from the American Cancer Society’s Cancer Action Network show that 73% of cancer survivors and patients worried about how they would pay for their cancer care, and 51% said they had medical debt due to treatment. For example, state-of-the-art cancer therapy can cost up to $1,000,000.

Texas A&M University and the University of Missouri are leading the effort to develop a low-cost, safe and controlled cancer treatment. 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 initiative, an effort to promote and increase funding for cancer research. It is one of the first projects funded by the newly created agency, which aims to accelerate better health outcomes for all by supporting the development of high-impact solutions to society’s most challenging health problems.

Quickly analyze cells

$12 million of the grant will go to the Texas A&M Engineering Experiment Station/Texas A&M, where co-principal investigators Drs. Arum Han, Jim Song, and Chelsea Hu develop synthetic programmable bacteria for immune-targeted killing in tumor environments (SPIKEs). The idea is to develop bacteria that help T cells kill cancerous tissue, destroy themselves once the cancer is gone, and leave the body safely as human waste.

SPIKEs can specifically target tumor cells. And because it only targets cancerous tissue and not the surrounding healthy cells, patient safety is increased exponentially. It is a great honor to be on this team and tackle a major health problem that affects many people.”

Arum Han, the Texas Instruments professor in the Department of Electrical and Computer Engineering

Han’s laboratory develops high-throughput microfluidic systems that can rapidly process and screen vast bacterial therapeutic libraries, cell by cell, to quickly identify the most promising treatments. These systems are made possible by integrating microfabrication methods and biotechnology to realize a picoliter volume liquid handling system that can accurately analyze single cells with high precision and high speeds, creating devices to rapidly analyze individual cells.

“The biggest challenge is figuring out how to actually develop these advanced microdevices that allow us to run millions and millions of fully automated tests without manual or human intervention,” Han said. “That’s the technical challenge.”

Rescuing 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 been working on immunotherapy against bacteria for the past five years. A certain bacteria known as Brucella melitensis can manipulate the human body microenvironment and promote T cell-mediated anti-tumor immunity to treat at least four types of cancer.

“We are working on improvement Brucella melitensis to more efficiently prevent or suppress tumor growth,” said Song, a professor at Texas A&M School of Medicine. “Our current approach involves figuring out how to engineer bacteria to rescue anti-tumor immune cells, thereby increasing their effectiveness in killing tumor cells.

‘That is evident from the data so far BrucellaIts efficiency is dramatically higher than that of other cancer treatments, such as chimeric antigen receptor T-cell therapy and T-cell receptor therapies, with a responsiveness of more than 70%,” said Song.

Safe and controllable therapies

While Song continues to test the bacteria’s efficiency using cancer models, Hu, an assistant professor in the Artie McFerrin Department of Chemical Engineering and a synthetic biologist, is working to ensure the live bacterial therapy is safe and controllable.

“The Brucella The strain we use has been shown to be safe for the hosts because it is an attenuated version, meaning an important gene necessary for bacterial virulence has been deleted,” Hu said. Ultimately, we want to control the speed of the bacteria. growth, where it grows within the tumor environment, and its ability to self-destruct when its mission is complete.”

To control growth rates, the bacteria’s genes will be adjusted to regulate the population and oscillate around a specific set point. Hu also plans to build biosensors into the bacteria, allowing them to distinguish between healthy tissue and tumor tissue, to ensure they grow only within the tumor microenvironment.

The bacterium will be engineered to have a receptor that ensures that once the cancer is gone, the patient can take antibiotics that signal the bacterium to cut itself up and be safely removed from the patient’s body.

“As humans, we are actually covered in bacteria, and many diseases are caused by an imbalance in these bacterial communities,” Hu said. “For example, while some people have incredibly fragile stomachs, others have robust stomachs. The science behind this is that people with a strong immune system and digestive system have a healthy community of bacterial cells in their intestines. There is a lot of potential in living therapies. .”

“It’s really a great opportunity to have an incredible team that has expertise and can push this technology to the front lines,” Hu said. “So that kind of goal is to reach the clinic and provide patients with effective cancer treatment for less than $1 per dose.”

Tackling difficult issues using unconventional approaches

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

“The three main advantages of this work are high safety, low cost and specific targeting of cancer tumors,” Han said. “We are very excited to be one of the first teams to receive support from ARPA-H, a brand new agency created and supported by Congress to really tackle tough problems across broad areas of healthcare. We attack difficult problems. problems using unconventional approaches. High risk and high impact is the hallmark of our approach.”

And the future applications of technical bacteria that this research opens up are limitless.

For our next big project, we will work together to develop bacteria against autoimmune diseases such as type 1 diabetes and rheumatoid arthritis,” Song said. Bacteria-based immunotherapy represents a groundbreaking frontier in medicine and offers the potential to revolutionize the treatment of autoimmune diseases. Now that we have harnessed the power of beneficial microbes to modulate the immune system, we are about to change the future of medicine. Our research and expertise hold the promise of transforming the lives of millions of people, offering them new hope and a healthier future.”