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<a href="https://2017.igem.org/Team:ETH_Zurich/Circuit/Fb_Contrast_Agent">Function B: MRI Contrast Agent</a></p> | <a href="https://2017.igem.org/Team:ETH_Zurich/Circuit/Fb_Contrast_Agent">Function B: MRI Contrast Agent</a></p> | ||
<p>Find out more about | <p>Find out more about | ||
− | <a href="https://2017.igem.org/Team:ETH_Zurich/Circuit/ | + | <a href="https://2017.igem.org/Team:ETH_Zurich/Circuit/Fc_Anti_Cancer_Toxin">Function C: Anti-Cancer Toxin</a></p> |
<details> | <details> |
Revision as of 06:02, 27 October 2017
![CATE logo](https://static.igem.org/mediawiki/2017/d/d6/T--ETH_Zurich--LogoMinimal.png)
CATE Treatment (Applied Design)
Overview
We envision the treatment with our novel bacterial cancer therapy - CATE, to follow the depicted strategy. A short duration, enhanced safety and overall effectiveness are expected to be decisive factors for choosing to treat with CATE instead of conventional therapies.
The following steps will guide you through the treatment:
1. Administration of the Bacterial Therapeutic
Following diagnostic procedures and the decision to use CATE, the patient will receive a soluble formulation of CATE in an intravenous injection. This is a quick and easy step for both the patient and the doctor.
2. Colonization of the Tumor Tissue
CATE distributes throughout the body and specifically populates the tumor tissue. Only in this special microenvironment, rich in nutrients and hidden from the immune system, CATE can grow to a high cell density.
Checkpoint 1
3. Tumor Sensing
Only in the tumor tissue, two conditions necessary to pass the safety Checkpoint 1 are present.
- The first condition is the high cell density of the bacteria, that CATE can only reach in tumors because of their unique micro-environment.
- The second condition is the presence of a high concentration of lactate, a molecule typically overproduced by cancer cells.
Only If these two conditions are satisfied, CATE will pass Checkpoint 1 and proceed to the next step.
Read more about how CATE can identify tumors: Function A: Tumor Sensor
4. Anti-Cancer Toxin and MRI Contrast Agent Production
To pass Checkpoint 1, cell density of the bacteria in the tumor has to be high enough to kill it. Once this has been achieved, CATE will start to produce an Anti-Cancer Toxin. However, the toxin will not be released yet. It will reside in CATE until the second checkpoint has been passed. At the same time, CATE will also produce an MRI Contrast Agent. This will allow the doctor to confirm through an MRI scan that the Toxin is ready and the bacteria have indeed colonized the correct location.
Find out more about Function B: MRI Contrast Agent
Find out more about Function C: Anti-Cancer Toxin
5. Magnetic Resonance Imaging
The patient is examined in an MRI machine and the doctor can inspect the location of CATE. Because the MRI Contrast Agent is produced together with the Anti-Cancer Toxin, the doctor can also be indirectly assured that enough of the Toxin is available to eradicate the tumor. This additional security step is unique to our bacterial cancer therapy with CATE. Neither conventional cancer treatments that include systemically administered toxic compounds, nor modern targeted therapies with engineered immune cells have the advantage of combining a molecular tumor-recognition with a location-approved toxicity-activation.
6. Focused Ultrasound
This step is directly coupled to Magnetic Resonance Imaging. Immediately after examining the MRI scan, the doctor can apply focused ultrasound specifically to the tumor site. Focused ultrasound is an emerging new medical technology that is already built in in modern MRI devices. It allows for high-energy sound waves outside of the audible spectrum (the same ones used by bats for navigation) to transmit their energy to a specific location in the inside of the body. This results in a temperature increase from 37°C to 45°C in a narrowly defined area of the tumor. It is applied to the tumor where CATE is present for 3 h.
Checkpoint 2
7. Heat Sensing
The change in the temperature, from 37°C to 45°C, caused by the doctor via focused ultrasound, alerts CATE that Checkpoint 2 has been passed due to the release of a protein that has been blocking the activation of the Heat Sensing circuit. Then CATE continues with the next step of the treatment procedure.
Find out more about Function D: Heat Sensor
8. Cell Lysis and Toxin Release
After successfully going through Checkpoint 2, CATE is designed to produce a special protein that originates from bacteria-killing phages. This protein interferes with the bacterial cell wall synthesis which leads to pore formation and ultimately, the breakdown of CATE. This way, the previously accumulated Anti-Cancer Toxin is released to the tumor tissue.
Find out more about Function E: Cell Lysis
9. Cancer Killing
After the Anti-Cancer Toxin gets released, it enters the malignant cells. Once inside, it interferes with the cell cycle through stabilization of a tumor-suppressor protein. This interference leads to the death of cancer cells through apoptosis. With this, CATE’s mission is accomplished.
Read more about Function C: Anti-Cancer Toxin