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Human Cells with ‘Built-in Genetic Circuit’ can impair ability of Cancer Cells to Survive and Grow, say Researchers

As tumours develop and grow, they rapidly outstrip the supply of oxygen delivered by existing blood vessels

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FILE - A biotechnician demonstrates the loading of a genome sequencing machine at the J. Craig Venter Institute in Rockville, Maryland. Relative to their ability to pay, cancer patients in China and India face much higher prices than wealthier U.S. patients. VOA
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London, Nov 26, 2016: Researchers have engineered cells with a “built-in genetic circuit” that produces a molecule that impairs the ability of cancer cells to survive and grow in their low oxygen environment.

The genetic circuit produces the machinery necessary for the production of a compound that inhibits a protein which has a significant and critical role in the growth and survival of tumours.

This results in the cancer cells being unable to survive in the low oxygen, low nutrient tumour micro-environment.

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“In a wider sense, we have given these engineered cells the ability to fight back — to stop a key protein from functioning in cancer cells,” said lead researcher Ali Tavassoli, Professor at the University of Southampton in Britain.

“This opens up the possibility for the production and use of sentinel circuits, which produce other bioactive compounds in response to environmental or cellular changes, to target a range of diseases including cancer,” Tavassoli said.

As tumours develop and grow, they rapidly outstrip the supply of oxygen delivered by existing blood vessels. This results in cancer cells needing to adapt to a low oxygen environment.

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To enable them to survive, adapt and grow in the low oxygen or ‘hypoxic’ environment, tumours contain increased levels of a protein called Hypoxia-inducible factor 1 (HIF-1).

This protein senses reduced oxygen levels and triggers many changes in cellular function, including a changed metabolism and sending signals for the formation of new blood vessels.

It is thought that tumours primarily hijack the function of this protein (HIF-1) to survive and grow.

“In an effort to better understand the role of HIF-1 in cancer, and to demonstrate the potential for inhibiting this protein in cancer therapy, we engineered a human cell line with an additional genetic circuit that produces the HIF-1 inhibiting molecule when placed in a hypoxic environment,” Tavassoli explained.

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“We’ve been able to show that the engineered cells produce the HIF-1 inhibitor, and this molecule goes on to inhibit HIF-1 function in cells, limiting the ability of these cells to survive and grow in a nutrient-limited environment as expected,” Tavassoli noted.

The genetic circuit was incorporated onto the chromosome of a human cell line, which encodes the protein machinery required for the production of their cyclic peptide HIF-1 inhibitor.

The research, published in the journal ACS Synthetic Biology, demonstrates the possibility of adding new machinery to human cells to enable them to make therapeutic agents in response to disease signals. (IANS)

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Decoded: How Cancer Cells Cripple Immune System

Anti-PD1 therapy blocks interaction between PD-1 -- a protein on the surface of T-cells -- and PD-L1, PD-1's counterpart molecule on tumour cells, thus reinvigorating T-cells and allowing them to unleash killing power on the tumour

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The research offers a paradigm-shifting picture of how cancers take a systemic approach to suppressing the immune system. Pixabay

Researchers have found that cancer cells send out biological “drones” to fight the immune system and survive.

The study showed that cancer cells release “drones” — small vesicles called exosomes circulating in the blood and armed with proteins called PD-L1 that cause T-cells to tire before they have a chance to reach the tumour.

The research offers a paradigm-shifting picture of how cancers take a systemic approach to suppressing the immune system.

In addition, it also points to a new way to predict which cancer patients will respond to anti-PD1 therapy that disrupts immune suppression to fight tumours.

“Immunotherapies are life-saving for many patients with metastatic melanoma, but about 70 per cent of these patients don’t respond,” said Guo Wei, Professor at the University of Pennsylvania.

“These treatments are costly and have toxic side effects so it would be very helpful to know which patients are going to respond,” Wei added.

Cancer
Representational image. Pixabay

Anti-PD1 therapy blocks interaction between PD-1 — a protein on the surface of T-cells — and PD-L1, PD-1’s counterpart molecule on tumour cells, thus reinvigorating T-cells and allowing them to unleash killing power on the tumour.

In the study, published in the journal Nature, the team found that exosomes from human melanoma cells also carried PD-L1 on their surface. Exosomal PD-L1 can directly bind to and inhibit T-cell functions.

Identification of the exosomal PD-L1 secreted by tumour cells provides a major update to the immune checkpoint mechanism, and offers novel insight into tumour immune evasion.

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According to the researchers, exosomes are tiny lipid-encapsulated vesicles with a diameter less than 1/100 of a red blood cell.

Since a single tumour cell is able to secrete many copies of exosomes, the interaction between the PD-L1 exosomes and T-cells provides a systemic and highly effective means to suppress anti-tumour immunity in the whole body. This may explain why cancer patients might have weakened immune system, they noted. (IANS)