Baylor Researchers Use Bacteria to Target & Kill Colorectal Cancer Cells

A surprising ally is entering the fight against colorectal cancer: common bacteria. Researchers at Baylor University have pioneered a novel approach, effectively turning Listeria monocytogenes – a bacterium often associated with foodborne illness – into a targeted drug delivery system. This isn’t about introducing infection, but rather harnessing the bacteria’s natural ability to enter cells to deliver a potent cancer-killing payload directly to tumor sites.

Harnessing a Natural Trojan Horse

The research, published in Cell Chemical Biology in December 2025, details how modified Listeria monocytogenes (LM) can be used to deliver saporin, a cytotoxin, directly into colorectal cancer cells. Led by Michael S. VanNieuwenhze, Ph.D., FRSC, University Distinguished Professor and chair of the Department of Biology at Baylor, the team demonstrated that this method significantly improved cytotoxicity – the ability to kill cancer cells – compared to conventional antibody-drug conjugates (ADCs) like SN38/Dox-ADC. Baylor News reports that this approach is particularly promising for microsatellite-stable (MSS) colorectal cancers, a subtype that often doesn’t respond well to existing immunotherapies.

Colorectal cancer is the third most common cancer diagnosed in the United States, with an estimated 153,020 new cases expected in 2024. MSS colorectal cancers account for a significant proportion of these cases, making the development of new treatment strategies for this subtype critically important.

How Does it Work? The Science Behind the Strategy

Listeria monocytogenes is a Gram-positive bacterium known for its ability to invade cells and thrive within them. Researchers have long explored its potential as a cancer vaccine platform, leveraging the immune response triggered by the bacteria. Even though, the Baylor team’s innovation lies in utilizing LM specifically as a vehicle for delivering cytotoxic drugs. The bacteria are engineered to carry saporin, a toxin that disrupts cell function, directly into the tumor cells.

The study found that LM delivery of saporin dramatically improved cytotoxicity in vitro (in laboratory cell cultures) and reduced tumor growth in vivo (in living organisms, specifically a mouse model of MSS colorectal cancer). Importantly, the reduction in tumor growth correlated with increased immune cell infiltration into the tumor, suggesting that the LM-delivered saporin not only kills cancer cells directly but also stimulates an immune response against the tumor.

Understanding Cytotoxins and Targeted Delivery

Cytotoxins are substances that are toxic to cells, often used in cancer treatment to kill rapidly dividing cancer cells. However, traditional chemotherapy can affect healthy cells as well, leading to side effects. Targeted drug delivery aims to minimize these side effects by delivering the cytotoxic drug specifically to the tumor, sparing healthy tissues. Antibody-drug conjugates (ADCs) are one example of targeted delivery, where a cytotoxic drug is attached to an antibody that recognizes a specific protein on cancer cells. However, ADCs can face challenges with target resistance and limited tumor penetration. The Baylor team’s approach with LM offers a potentially more effective way to overcome these hurdles.

Study Details and Limitations

The research involved both in vitro experiments using human colorectal cancer cell lines and in vivo experiments using a mouse model of MSS colorectal cancer. The team compared the efficacy of LM-delivered saporin to that of a conventional ADC (SN38/Dox-ADC). Key findings included significantly improved cytotoxicity with LM-saporin and reduced tumor growth in the mouse model.

It’s crucial to note the limitations of this study. The research was conducted in a preclinical setting, meaning it was performed in cell cultures and animals, not humans. While the results are promising, they do not guarantee that the same effects will be observed in human patients. Further research, including clinical trials, is necessary to evaluate the safety and efficacy of this approach in humans. The study also focused specifically on MSS colorectal cancer; it remains to be seen whether this approach will be effective for other subtypes of colorectal cancer.

What Does This Imply for Patients?

This research represents a significant step forward in the development of novel therapies for colorectal cancer, particularly for patients with MSS tumors who may not respond well to existing treatments. The concept of using bacteria to deliver drugs is not entirely new, but the Baylor team’s work demonstrates the potential of LM as a highly effective delivery vehicle for cytotoxins.

However, it’s important to emphasize that this is still early-stage research. It will likely be several years before this approach is available as a treatment option for patients. The next steps involve conducting rigorous clinical trials to assess the safety and efficacy of LM-delivered saporin in humans. These trials will need to carefully evaluate potential side effects and determine the optimal dosage and delivery method.

The Path Forward: Clinical Trials and Beyond

The Baylor University team has already filed a patent application (WO 2024/054673) related to this technology, indicating their commitment to further developing and commercializing this approach. The immediate next step is to secure funding for clinical trials. These trials will likely begin with compact groups of patients with advanced MSS colorectal cancer who have exhausted other treatment options.

If the clinical trials are successful, this approach could potentially be combined with other cancer therapies, such as immunotherapy, to further enhance treatment outcomes. Researchers are also exploring the possibility of using LM to deliver other types of drugs to different types of cancer. The versatility of this delivery system makes it a promising area of research with the potential to revolutionize cancer treatment.

Ongoing surveillance and monitoring of clinical trial data will be crucial to identify any potential safety concerns and optimize treatment protocols. The results of these trials will inform future guidance and recommendations for the use of LM-delivered cytotoxins in the treatment of colorectal cancer.