5 ms·

I may be missing something but the article does not explain how the bacteria target is actually targeting the cancer cells. Of course, if you can design an idea

I may be missing something but the article does not explain how the bacteria target is actually targeting the cancer cells. Of course, if you can design an ideal universal cancer targeting mechanism, the active ingredient itself is beside the point. Did anyone else catch this? Stopping DNA replication across the body will be fatal. This is what eventually kills with radiation toxicity.

asdff 4y ago
It does, from the article: "“Normally, our blood vessel walls are all sealed pipes,” Brahmbhatt says. “But around wherever the cancer is growing, the blood vessels are known to be very defective. They have got a lot of holes in them.” Brahmbhatt and his collaborator Jennifer MacDiarmid devised a clever ploy. They would send a Trojan horse into malignant cells and turn cancer’s own trickery against it. The Trojan horse, in this case, is a product of a harmless bacteria that’s been genetically engineered to have specific qualities. When this genetically engineered bacteria divides, it yields a tiny non-living cell of 400 nanometers in diameter—the right size to slip through the damaged vessels and mingle with the tumors."
- yshrestha 4y ago
  I see. I do wonder how specific that is though. Potentially it could be toxic to other areas where vasculature could be "leaky". Like in the filtration mechanisms in the kidney. Targeting the cancer's vascular supply is also a known anti-cancer mechanism of action (anti-angiogenics). How will this method not have the same toxicity as that one?
  - asdff 4y ago
    Presumably that 400nm size is important for specificity as well
pazimzadeh 4y ago
The article is missing lots of detail. They use antibodies to target receptors which are highly expressed by tumors, such as Epidermal growth factor receptor (EGFR). "Given that the EDV surface is coated with lipopolysaccharide (LPS), single-chain bispecific antibodies were attached to the EDV surface where one arm of the antibody is directed to the O-polysaccharide epitopes and the other arm is directed to a tumour cell surface receptor for example Epidermal growth factor receptor (EGFR) which is found on the surface of over 70% of solid tumours" and "The EDVs being 400 nm rapidly fall out of these fenestrations and enter into the tumour microenvironment and since they carry the bispecific antibody on the EDV surface, the anti-EGFR component binds to EGFR on the tumour cell surface. This provokes macropinocytosis and the EDVs are taken into the early endosomes, followed by lysosomes and broken down in these organelles releasing the drug PNU-159682. The drug enters into the tumour cell cytoplasm and the nucleus and intercalates with the chromosomal DNA resulting in tumour cell apoptosis. In the event that a tumour type does not express EGFR for example liver cancer, which expresses asialoglycoprotein, then the bispecific antibody can be changed to anti-asialoglycoprotein while the anti-O-polysaccharide component remains constant. Similarly, HER-2 positive breast cancers can be targeted via anti-HER2/anti-O-polysaccharide bispecific antibody" https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.1111/1751-7915.13952 https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.111... I don't think this particular therapeutic automatically homes to all cancer cells. However, certain bacteria have been found to home to cancer cells, so maybe that helps too. https://wis-wander.weizmann.ac.il/life-sciences/cells-inside-cells-bacteria-live-cancer-cells https://wis-wander.weizmann.ac.il/life-sciences/cells-inside...
- yshrestha 4y ago
  Ah. Thanks for finding this. That makes more sense. Bacteria that are attracted to cancer cells are a fascinating concept. It is very exciting to see another tool in the toolbox to achieve higher cancer cell therapeutic specificity.

asdff 4y ago

It does, from the article: "“Normally, our blood vessel walls are all sealed pipes,” Brahmbhatt says. “But around wherever the cancer is growing, the blood vessels are known to be very defective. They have got a lot of holes in them.” Brahmbhatt and his collaborator Jennifer MacDiarmid devised a clever ploy. They would send a Trojan horse into malignant cells and turn cancer’s own trickery against it. The Trojan horse, in this case, is a product of a harmless bacteria that’s been genetically engineered to have specific qualities. When this genetically engineered bacteria divides, it yields a tiny non-living cell of 400 nanometers in diameter—the right size to slip through the damaged vessels and mingle with the tumors."

yshrestha 4y ago
I see. I do wonder how specific that is though. Potentially it could be toxic to other areas where vasculature could be "leaky". Like in the filtration mechanisms in the kidney. Targeting the cancer's vascular supply is also a known anti-cancer mechanism of action (anti-angiogenics). How will this method not have the same toxicity as that one?
- asdff 4y ago
  Presumably that 400nm size is important for specificity as well

pazimzadeh 4y ago

The article is missing lots of detail. They use antibodies to target receptors which are highly expressed by tumors, such as Epidermal growth factor receptor (EGFR). "Given that the EDV surface is coated with lipopolysaccharide (LPS), single-chain bispecific antibodies were attached to the EDV surface where one arm of the antibody is directed to the O-polysaccharide epitopes and the other arm is directed to a tumour cell surface receptor for example Epidermal growth factor receptor (EGFR) which is found on the surface of over 70% of solid tumours" and "The EDVs being 400 nm rapidly fall out of these fenestrations and enter into the tumour microenvironment and since they carry the bispecific antibody on the EDV surface, the anti-EGFR component binds to EGFR on the tumour cell surface. This provokes macropinocytosis and the EDVs are taken into the early endosomes, followed by lysosomes and broken down in these organelles releasing the drug PNU-159682. The drug enters into the tumour cell cytoplasm and the nucleus and intercalates with the chromosomal DNA resulting in tumour cell apoptosis. In the event that a tumour type does not express EGFR for example liver cancer, which expresses asialoglycoprotein, then the bispecific antibody can be changed to anti-asialoglycoprotein while the anti-O-polysaccharide component remains constant. Similarly, HER-2 positive breast cancers can be targeted via anti-HER2/anti-O-polysaccharide bispecific antibody" https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.1111/1751-7915.13952 https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.111... I don't think this particular therapeutic automatically homes to all cancer cells. However, certain bacteria have been found to home to cancer cells, so maybe that helps too. https://wis-wander.weizmann.ac.il/life-sciences/cells-inside-cells-bacteria-live-cancer-cells https://wis-wander.weizmann.ac.il/life-sciences/cells-inside...

yshrestha 4y ago
Ah. Thanks for finding this. That makes more sense. Bacteria that are attracted to cancer cells are a fascinating concept. It is very exciting to see another tool in the toolbox to achieve higher cancer cell therapeutic specificity.