Hacking bacteria to fight cancer - Tal Danino
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In 1884, an unlucky patient who had a rapidly growing cancer in his neck came down with an unrelated bacterial skin infection. As he recovered from the infection, the cancer surprisingly began to recede. The infection had stimulated the patient’s immune system. Today, synthetic biologists program bacteria to safely deliver drugs directly to tumors. How is this possible? Tal Danino investigates.
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Bacteria have the natural ability to sense their surrounding environment and grow inside the human body. Using synthetic biology tools, scientists can program bacteria to deliver drugs to disease sites such as cancer. Can such programed bacteria act as personalized living medicines to help advance human health?
Some cancer cells find ways to hide from the body’s immune cells. One of the common tricks cancer cells use is by making a protein called CD47. This protein stays on the surface of the cancer cells and sends a “D on’t eat me” signal to immune cells. So, the immune cells do not attack the cancer cells.
To address this problem, scientists have developed antibodies that can bind to this CD47 protein masking the “Don’t eat me” signal so the immune cells can attack and eliminate the cancer cells. But bacteria cannot be engineered to make normal and effective antibodies for CD47.
Dr. Michael Dougan and his colleagues at Massachusetts General Hospital in Boston developed a smaller version of the molecule called a nanobody. Interestingly, these nanobodies are tiny enough for the bacteria to make and they are more potent that traditional antibodies.
Drs. Tal Danino and Nicholas Arpaia at Columbia University in New York inserted nanobody genes inside a type of bacteria equipped with synchronized lysis circuit. Then large numbers of this bacteria were grown and injected in mouse tumors. Inside the mouse tumor, the bacteria multiplied happily. As the synchronized lysis circuit was programmed for mass self-destruction, the majority of the bacteria ripped themselves apart spilling out nanobodies that bound to the CD47 on cancer cells. The camouflage of the cancer cells was compromised, and immune cells killed the tumor.
Interestingly, once the tumor that received direct injection of bacteria shrank, other tumors in other parts of the mice also reduced in size. There is a possibility that the bacteria not only attracted the immune cells to kill the tumor where they were injected, but also, they taught the immune system to recognize similar types of tumors in other parts of the mice.
Further reading
-NYT : https://www.nytimes.com/2019/07/03/science/cancer-bacteria-immune-system.html
-TED talk: https://www.ted.com/talks/tal_danino_we_can_use_bacteria_to_detect_cancer_and_maybe_treat_it?language=en
-Danino lab: http://daninolab.nyc/
Some cancer cells find ways to hide from the body’s immune cells. One of the common tricks cancer cells use is by making a protein called CD47. This protein stays on the surface of the cancer cells and sends a “D on’t eat me” signal to immune cells. So, the immune cells do not attack the cancer cells.
To address this problem, scientists have developed antibodies that can bind to this CD47 protein masking the “Don’t eat me” signal so the immune cells can attack and eliminate the cancer cells. But bacteria cannot be engineered to make normal and effective antibodies for CD47.
Dr. Michael Dougan and his colleagues at Massachusetts General Hospital in Boston developed a smaller version of the molecule called a nanobody. Interestingly, these nanobodies are tiny enough for the bacteria to make and they are more potent that traditional antibodies.
Drs. Tal Danino and Nicholas Arpaia at Columbia University in New York inserted nanobody genes inside a type of bacteria equipped with synchronized lysis circuit. Then large numbers of this bacteria were grown and injected in mouse tumors. Inside the mouse tumor, the bacteria multiplied happily. As the synchronized lysis circuit was programmed for mass self-destruction, the majority of the bacteria ripped themselves apart spilling out nanobodies that bound to the CD47 on cancer cells. The camouflage of the cancer cells was compromised, and immune cells killed the tumor.
Interestingly, once the tumor that received direct injection of bacteria shrank, other tumors in other parts of the mice also reduced in size. There is a possibility that the bacteria not only attracted the immune cells to kill the tumor where they were injected, but also, they taught the immune system to recognize similar types of tumors in other parts of the mice.
Further reading
-NYT : https://www.nytimes.com/2019/07/03/science/cancer-bacteria-immune-system.html
-TED talk: https://www.ted.com/talks/tal_danino_we_can_use_bacteria_to_detect_cancer_and_maybe_treat_it?language=en
-Danino lab: http://daninolab.nyc/
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Meet The Creators
- Educator Tal Danino
- Director Chris Bishop
- Narrator Addison Anderson
- Animator Chris Bishop
- Assistant Animation and Compositing Melissa Ferrari, Ariel Navas
- Director of Production Gerta Xhelo
- Editorial Producer Alex Rosenthal
- Associate Producer Bethany Cutmore-Scott
- Script Editor Alex Gendler
- Fact-Checker Joseph Isaac
- Special Thanks Sreyan Chowdhury, Dhruba Deb, Tiffany Chien
