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Reprogramming cancer cells as immune defenders

Reprogramming cancer cells into immune defenders
Dolly the sheep decides the future of Felipe Pereira’s career. Choosing between becoming an architect or a scientist, one of the world’s most extreme examples of cellular programming sparked his curiosity about the human body. Photo Credit: Johan Persson

Filipe Pereira and his colleagues hope to improve current cancer treatments by reprogramming tumor cells to become the body’s defenders. Right now, some of the most important players in the immune system, dendritic cells, are patrolling your body to Look for foreign objects. If they find something suspicious, they break it down into smaller fragments called antigens, which are presented to the body’s lymphocytes, also known as the immune system’s killer cells. This is how killer cells learn which threats to look for and fight.

What if it was possible to generate dendritic cells? Lund University professor Pereira decided to give it a try. The nucleus of a somatic cell (all cells except gametocytes) contains all the information a cell needs to develop into any other cell. A cell’s fate depends on which genes are expressed in the nucleus. If we tweak gene expression, we can turn one cell into a completely different cell. The challenge is knowing which molecules need to be added to reprogram the cell exactly the way you want. It was from this concept of reprogramming that I decided to deal with dendritic cells,” says Pereira. In 2018 and 2022, Pereira and his research group published their findings: It is possible to transform mouse and human connective tissue into Cells (such as skin cells) are reprogrammed into immune defenders – the code of dendritic cells.

The three Trojan horse molecules turned out to be the answer The process of reprogramming cells into dendritic cells with the ability to detect and present antigens in the same manner as native dendritic cells takes eight days. “We managed to add three molecules, called transcription factors. I usually call these molecules the ‘three Trojan horses,'” Pereira said. But as cancer cells divide and mutate, they manage to hide themselves. So the cancer cells evade detection, which means the dendritic cells can’t do their job. .

Yet Pereira had an idea. If these molecules could be used to reprogram cancer cells into dendritic cells So what? In other words, a gene therapy for cancer.

“Normally, when we talk about gene therapy, we Refers to the correction of a faulty or damaged gene in a person. Instead, here we refer to using gene therapy to reprogram cancer cells to force them to unmask themselves,” Pereira said.

patrolling cells found tumor cells

How does it work? Using these three Trojan horse molecules, cancer cells are reprogrammed into dendritic cells, revealing the tumor’s true identity to the immune system. The strategy It is possible to improve existing cancer therapies, such as immune checkpoint therapy (winner of the 2018 Nobel Prize in Physiology or Medicine). Simply put, this involves blocking the molecular brakes that prevent killer cells from doing their job. This allows the immune system to attack Fights cancer cells. Pereira specializes in malignant melanoma and head and neck cancers, which are known to have moderate to high mutation rates. “New checkpoint therapy is effective in 20-30% of patients with malignant melanoma. We hope our findings will complement this treatment and make it more effective,” Pereira said. This is an advantage if the tumor has already accumulated mutations.

“When tested in mice, we looked Most of the 15 tumors treated mice showed slowed growth. Two of the mice were completely cured. This makes us want to go a step further, and we hope to be in clinical trials within a few years, even if the path ahead is not entirely straightforward,” Pereira said. All viral components that can cause disease and the ability to replicate.

Pereira believes that the growing enthusiasm for gene therapy is due to the recent success in the field.

” It offers hope to patients suffering from conditions that cannot be treated with current conventional therapies . At the same time, there are many challenges. The regulatory framework for these new therapies is not yet in place, and manufacturing is demanding and costly, often higher than traditional drug development. But as I like to say, if it was easy, it would have been done long ago. Yeah? said Pereira.

Quote: Reprogramming Cancer Cells into Immune Defenders (2022, December 22) Accessed January 11, 2023 from https://medicalxpress.com/ news/2022-12-reprogramming-cancer-cells-immune-defenders.html Retrieve

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