The cost of advanced cancer treatments can be extremely high, making them inaccessible for a significant portion of the population. Even Photodynamic therapy, often viewed as a relatively affordable choice when compared with techniques such as CAR-T cell Therapy, Radioembolization or Proton Beam Therapy, proves to be expensive due to the necessity of delivering external light to the patient through lasers, light-emitting diodes (LEDs), or lamps.

Perhaps the biggest limitation of using PDT to combat cancer is the light source, as visible light cannot adequately penetrate the human body. PDT is not a viable option for targeting cancers located deeply within the human body, and that’s why, so far, PDT is mainly used for the treatment of skin cancer or other types of cancers, located on or just below the skin's surface.

Building upon these barriers, our team strived to introduce a machine that turns traditional, equipment-based PDT into an accessible, easily administered and cost-effective tool for targeting all kinds of solid tumors.

We envision IRIS integrated into an injectable tool, able to perform PDT without the need of external light administration. This approach eliminates the need for expensive equipment and energy-intensive procedures, therefore making it more affordable and highly accessible to communities worldwide.

But how can this bacteria strain serve as a therapeutic tool?

The key aspect of that matter is time. Our proposal of using IRIS as a therapeutic tool consists of three major chronical events taking place inside the patient’s body:

IRIS is designed to serve as a general PDT tool, targeting all kinds of solid tumors in the human body. As breast, lung and colorectal cancer are the most frequent cancer types worldwide ^[1], we indicate examples of how IRIS can be utilized as a therapeutic solution for these specific types of cancer.



We, therefore, suggest that the mechanism should take place in two steps: injection of the genetically engineered bacteria, IRIS (I), followed by the injection of Methoxy e-Coelenterazine (IRIS II). IRIS is designed to serve as a general PDT tool, targeting all kinds of solid tumors in the human body. As breast, lung and colorectal cancer are the most frequent cancer types worldwide, we indicate examples of how IRIS can be utilized as a therapeutic solution for these specific types of cancer.

But is this method safe for the patient?

Of course, to achieve the safe implementation of our project in real-case scenarios, many measures need to be taken. In our opinion the first steps that need to be taken for IRIS’ application to come true are:

1. Drug Delivery system (DDS)

Although Bacteria Mediated Tumor Therapy exists and has even been tested on animal models, some can claim that directly injecting bacteria in a person’s body can trigger endogenous immune responses. The bacteria are likely to be recognized as threats, and that could lead to immune activation (leukocytes, such as neutrophils and macrophages are recruited to the site of infection to destroy the bacteria) or an inflammatory response (swelling, redness, heat and pain) at the injection site.

Our solution to that issue is the utilization of drug delivery systems. DDSs are widely used as carriage systems for targeted drug delivery. Many DDSs, such as liposomes, dendrimers and nanomaterials like polymeric nanoparticles and carbon nanotubes, are available.

Liposomes, for example, can be used to deliver IRIS directly to the target tumor site, where a triggered release of the bacteria could take place. In that way, the bacteria are not going to directly interact with the patient and possible immune responses can be avoided.

2. Adhesive Proteins

Our engineered E.coli bacteria can, for a fact, proliferate within hypoxic cancerous environments, as they are facultative anaerobes and tumor-sites are highly nutrient, offering optimal conditions for their proliferation. But optimal conditions can be found in other sites too. That could possibly lead to cytotoxicity of natural, healthy cells, causing side-effects. That’s why delivering IRIS directly to its target is an important issue that requires yet another solution.

A possible solution proposed by us, is incorporating specific adhesive proteins into IRIS, specifically designed to detect and bind to cancer cells. These proteins can even be expressed by the bacteria themselves.

By introducing these synthetic adhesins into our engineered E.coli chassis, which lacks the natural adhesins, specific adhesion of the bacteria to tumor cells can be achieved. The synthetic adhesins could, therefore, act as a tool for precise recognition and binding, facilitating potential applications in targeting tumor cells.

3. Quorum Sensing System

Delivery of IRIS to the target site is one aspect. But what happens with the time scheduling for the expression of IRIS’ genes? We don’t want the inserted genes to be expressed while the bacteria are still being delivered to the tumor. These genes should be expressed when the bacteria are located and proliferating in the tumor site, so that PpIX is accumulated in cancer cells.

To address this matter, we propose the employment of a Quorum Sensing System. Under quorum-sensing-control, the expression of IRIS’ genes within the tumor microenvironment is going to begin once the bacterial population reaches a certain threshold. Quorum Sensing, can for example regulate the expression of T7 RNA Polymerase, the basic regulatory element of our genes, since they are all expressed under T7 promoters. For that concept to take place, the final bacteria chassis used for the expression of our genes, should not contain any T7 RNA Polymerase gene.

4. Kill switch mechanism

In order to make IRIS a safer project, thus increasing the possibilities for it to be used in real-case scenarios, a kill switch mechanism can also be employed.

The main goal of this mechanism would be to eliminate the bacteria once they have successfully performed PDT. The bacteria would be genetically modified to generate a self-destructive element, such as a toxin, when certain events take place. For example, a population-based mechanism or a substance released after the cellular death of cancer cells could induce the toxin’s expression. In that way, our bacteria are not going to accumulate in the body, therefore, lowering the chances for side-effects or other possible threats for the patient.

Given the fact that co-overexpressing IRIS with cancer cells proves our concept, this sets the threshold for moving from the in-vitro stage, to in-vivo experiments. Of course, in order to perform in-vivo experiments, compliance with ethical standards and approval from regulatory authorities must be taken into account.

The first in-vivo experiments would be conducted on animal models, to check that everything is under control, before scaling up to human trials. All these events may sound pretty ambitious, but in the long term, our project is driven by the ultimate goal of creating a profound impact in the field of cancer treatment globally.

Photodynamic Therapy (PDT) and Bacteria-Mediated Tumor Therapy (BMTT) have not been used in a single project yet.

Our team envisions a revolutionary approach to solid tumor therapy, where IRIS, a genetically engineered machine conducts PDT directly within the tumor's microenvironment, eliminating the reliance on external light sources or other parameters. That is a groundbreaking development in cancer treatment, and our team aspires to witness it being widespread adopted and further developed on a global scale.

We have already established a few valuable connections with professors and medical experts specializing in the field of cancer. These collaborations have been significantly helpful for our better understanding of how our project can be applied successfully on real-case scenarios. We are committed to maintaining active engagement with the medical community, so that we can also gather valuable insights, refine our techniques, and validate the effectiveness of our treatment in controlled laboratory settings in the future.

In-vivo experiments are going to evaluate the efficacy, safety, and potential side effects of our treatment in a real clinical setting. Results derived from these trials will be instrumental in refining our approach and demonstrating its effectiveness in treating cancer in human subjects.

In the long term, our vision extends beyond research and development. We aim to establish strategic partnerships with pharmaceutical companies, biotechnology firms, and medical institutions to facilitate the production, distribution, and administration of our treatment on a larger scale. These collaborations will ensure that our innovative approach reaches patients in need and has a tangible impact on combating cancer worldwide.