Bugs deliver drugs: weaponizing bacteria to target colorectal cancer therapy
An innovative new drug delivery approach uses modified bacteria to target colorectal cancer.
Researchers from Baylor University, Texas Tech University Health Sciences Center (both TX, USA) and Indiana University (IN, USA) have engineered the bacterium Listeria monocytogenes to deliver saporin, a known cancer-killing toxin, to tumor cells. With demonstrable success in reducing tumor growth in mouse models of colorectal cancer, the feat could represent a promising avenue for new therapies, including bacteria-based anticancer vaccine strategies.
Targeted drug delivery is one of the fastest-growing fields in cancer therapy, and there is increasing interest in using bacteria for this purpose. The food-borne bacterium Listeria monocytogenes is particularly suited to this, as it can be modified for therapeutic purposes while maintaining its ability to penetrate human cells. Despite its potential, L. monocytogenes has yet to achieve clinical approval for the treatment of cancer in humans, meaning there is room for further development of novel therapies that utilize its unique characteristics to reduce tumor burden and positively impact patient lives.
In this spirit, the team designed two new bacteria-based drug delivery approaches targeting tumors.
“What if we could hook saporin on the surface of a bug and let the bug get delivered into the cell as it normally would?” study author Michael S. VanNieuwenhze mused. “We could then take advantage of chemistry inside the cell to release saporin to kill the cancer cell. That, in a nutshell, is what we were doing, and we were able to get it to work.”
Biocompatible bubble bots treat bladder tumors in mice
Researchers have developed simple ‘bubble bot’ microrobots for drug delivery, successfully treating bladder tumors in mouse models.
In one approach, they covalently attached saporin to the bacteria’s surface, while the other involved non-covalent attachment of antibody-drug conjugates. Drug delivery was targeted to endolysosomal and cytoplasmic cell compartments.
As a proof-of-concept, the team used fluorescent imaging to confirm that the saporin was definitely attached to the bacteria and that it could be carried into tumor cells. Then, they performed in vitro experiments, demonstrating that saporin delivery resulted in increased cytotoxicity.
Meanwhile, in vivo studies in a murine subcutaneous microsatellite-stable colorectal cancer model revealed that tumor growth was significantly reduced by L. monocytogenes-mediated delivery of saporin.
Taken together, these findings suggest that L. monocytogenes enabled controlled drug delivery within cancer cell compartments, which subsequently reduced the colorectal tumor burden. What’s more, no off-target toxicity was recorded.
The researchers now hope to build on this foundation, investigating genetic strategies that could make the process safer and more scalable. Ultimately, the goal is to get bacteria-based cancer therapies into the clinic, starting with L. monocytogenes and colorectal cancer.
“Overall, this study introduces a promising strategy of [L. monocytogenes]-based therapy with the potential to synergize with existing [L. monocytogenes]-based anticancer vaccine strategies,” they write in their conclusion. “These delivery approaches expand the repertoire of available treatment options using [L. monocytogenes] and are applicable with a wide variety of cancer types and anticancer payloads.”