$1 Cancer Treatment: Engineered Bacteria Breakthrough

What if a single one-dollar dose was capable of curing cancer?

A multi-university team of researchers is developing a highly efficient bacterial therapy for cancer treatment, which is safer with a single $1 dose.

Cancer medicines have always been ineffective in treating patients. Some, such as radiation and chemotherapy, have hazardous side effects, while others have low patient responsiveness, not to mention the cost of treatment. According to the American Cancer Society Cancer Action Network, 73% of cancer survivors and patients were concerned about how they would pay for their cancer care, and 51% were in medical debt as a result of treatment. For example, cutting-edge cancer treatment can cost up to $1,000,000.

The University of Missouri and Texas A&M University are spearheading the charge to develop a low-cost, safe, and controlled cancer treatment. The Advanced Research Projects Agency for Health (ARPA-H) awarded researchers a $20 million grant to fight cancer. The four-year project is part of the current administration’s Cancer Moonshot strategy, which aims to promote and expand cancer research funding. It is one of the first initiatives financed by the newly formed organization, which aims to accelerate better health outcomes for all by fostering the creation of high-impact solutions to society’s most difficult health problems.

Rapidly analyzing cells

Drs. Arum Han, Jim Song, and Chelsea Hu are co-principal investigators at the Texas A&M Engineering Experiment Station/Texas A&M, where they are developing synthetic programmable bacteria for immune-directed killing in tumor settings (SPIKEs). The plan is to design bacteria that will aid T cells in killing malignant tissue, then destroy itself once the cancer has been removed and leave the body safely as human waste.

SPIKEs can specifically target tumor cells. And since it’s only targeting cancerous tissue and not the surrounding healthy cells, the safety of the patient is exponentially increased. It’s a great honor to be on this team, tackling a major health problem that affects a lot of people.”

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

Han’s lab is working on high-throughput microfluidic systems that can process and screen huge bacterial therapeutic libraries one cell at a time, allowing them to swiftly discover the most promising treatments. These technologies are made possible by combining microfabrication methods and biotechnology to create a pico-liter-volume liquid handling device capable of accurately analyzing single cells with high precision and speed.

“The major challenge is figuring out how to actually develop these sophisticated microdevices that allow us to conduct millions and millions of fully automated tests with almost no manual or human intervention,” Han said. “That’s the engineering challenge.”

Rescuing anti-tumour immune cells

Song, an immunologist with a background in microbial pathogenesis, T cell biology, and T cell-based immunotherapy, has been working on bacteria immunotherapy for the past five years, while Han innovates and manufactures microdevices. To cure at least four forms of cancer, a bacteria called Brucella Melitensis can modify the human body’s microenvironment and enhance T cell-mediated anti-tumor immunity.

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

“Data so far shows that Brucella‘s efficiency is dramatically higher than other cancer treatments, such as Chimeric antigen receptor T cell therapy and T-cell receptor therapies, with a more than 70% responsiveness rate,” Song said.

Safe and controllable therapeutics

While Song continues to investigate the bacteria’s efficacy in cancer models, Hu, a synthetic biologist and assistant professor in the Artie McFerrin Department of Chemical Engineering, is striving to ensure the living bacterial therapy is safe and manageable.

“The Brucella strain we’re using has been shown to be safe for the hosts because it is an attenuated version, meaning a key gene that is required for bacteria virulence has been deleted,” Hu said. “Ultimately, we want to control the bacterium’s rate of growth, where it grows within the tumor environment, and its ability to self-destruct when its mission is completed.”

The bacterium’s genes will be tweaked to govern its population and oscillate around a specified setpoint in order to control its growth rate. Hu also intends to incorporate biosensors into the bacteria, allowing them to distinguish between healthy and malignant tissues and flourish only within the tumor microenvironment.

The bacterium will be developed to have a receptor, allowing the patient to take antibiotics that will signal the bacterium to essentially cut itself into pieces and be safely removed from the patient’s body after the cancer is gone.

“As humans, we’re actually covered in bacteria, and a lot of diseases are caused by an imbalance in these bacterial communities,” Hu said. “For instance, while some people have incredibly fragile stomachs, others have robust ones. The science behind it is that those people with strong immune and digestive systems have a healthy community of bacterial cells in their gut. There’s a lot of potential in living therapeutics.”

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

Attacking difficult issues using unconventional approaches

Dr. Zhilei Chen of Texas A&M Health Science Center and Dr. Xiaoning Qian of the Department of Electrical and Computer Engineering are also collaborators, as is Dr. Paul de Figueiredo of Missouri University.

“The three key advantages to this work are high safety, low cost and specific targeting of cancerous tumors,” Han said. “We are very excited that we are one of the first teams that are getting support from ARPA-H, which is a brand-new agency established and supported by Congress to really tackle hard problems in broad areas of health. We’re attacking difficult issues using unconventional approaches. High risk, high impact is the hallmark of our approach.”

And the possibilities for future uses of engineering bacteria that this research opens up are endless.

“For our next big project, we will work together to engineer bacteria against autoimmune diseases such as type 1 diabetes and rheumatoid arthritis,” Song said. Bacterium-based immunotherapy represents a groundbreaking frontier in medicine, offering the potential to revolutionize the treatment of autoimmune diseases. With the power of beneficial microbes harnessed to modulate the immune system, we are on the verge of changing the future of medicine. Our research and expertise hold the promise of transforming the lives of millions of people, providing them with new hope and healthier tomorrows.”