Current Cancer Treatments

Today, there are several approaches to treating cancer. In general, they can be divided into two main groups: local and systemic treatment options. Local treatment options include surgery and radiation therapy, while systemic options refer to chemotherapy, targeted therapy and immunotherapy. Typically, the patient will receive a combination of different treatments extended over several weeks to months. [2]

Some of the therapeutic options mentioned above are well established and have been used for decades, while others represent pioneering treatments developed thanks to advances in biological engineering. However, as seen from the list of pros and cons, no strategy is perfect. Therefore, complete removal of cancer without inflicting damage on the healthy tissue remains a challenge. [8]

Bacteria in Cancer Therapy

To tackle the challenge of treating cancer, we decided to look beyond these more established approaches and from the point of view of a synthetic biologist. Our search led us to the concept of bacterial cancer therapy - a strategy for treating cancer that actually dates back to the beginning of the 20th century but has since changed significantly. In the beginnings, different species of unmodified bacteria were given intravenously to cancer patients and were shown to accumulate preferentially in the tumorous tissue. [9] This attractive inherent feature has been investigated since and is thought to be due to a combination of mechanisms, including:

• entrapment of bacteria in the chaotic vasculature of the tumor,
• production of chemotactic agents in the tumor microenvironment and
• protection from the immune system that the microenvironment, as an immuno-privileged site, offers. [10]

Although native cytotoxicity of the bacteria was shown to inhibit tumor growth to a certain extent, simply administering unchanged bacteria intravenously has been connected to severe side effects and limited efficacy. [11] To overcome this, engineering efforts have been made and different modifications have been implemented and are currently being tested in clinical trials. [12] [13] However, full potential of bacteria as an anti-cancer agent has not yet been fulfilled.

Our vision

The ideal bacterial cancer therapeutic should be: [5]

• a tiny programmable robot factory that specifically targets tumors,
• selectively cytotoxic to cancer cells,
• self-propelled,
• responsive to external signals,
• able to sense the local environment and finally,
• externally detectable.

CATE, the cancer-targeting E. coli that we have engineered, represents our vision of the ideal bacterial cancer therapeutic. With the combination of autonomous targeting, visualization and externally controlled toxin release, we believe our project provides a novel non-invasive, quick and safe approach to treating cancer (Figure 2).