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Reprogramming Cells to Seek and Destroy Brain Cancer

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A new type of cell that can seek and destroy brain cancer and then dispose of themselves has just been successfully tested in mice. The cells are able to home in on brain tumors and reduce them to between 2 to 5% of their original size[1].

This new approach could potentially give doctors a new weapon against aggressive cancers like brain cancer (glioblastoma), which normally kills in 12-15 months.

Interestingly, it only took the researchers four days to create and deploy these cells in the mice, which is an amazing accomplishment.

As we have mentioned in previous articles, the approach of reprogramming cells in situ to combat diseases is gaining traction in the research community. Earlier this year, a study saw researchers change astrocytes (a common type of brain cell) into dopamine-producing neurons to replace the losses caused by Parkinson’s.

Homing in on cancer

Glioblastomas are particularly difficult cancers to treat as they are very challenging to remove from the brain. They spread through the brain creating a complex network of cancer cells, somewhat like a spider web, and this is what makes it almost impossible to extract safely.

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As glioblastomas grow, they give off signals that tell the body there is an injury, and so the immune system sends in roaming stem cells that detect these signals to make repairs. Stem cells are cells able to create various types of specialized cells on demand, and can be thought of like the Swiss army knives of the cell world.

The research team here believe they can take advantage of stem cells and their ability to detect injury signals that allow them to home in on cancer cells. They could adapt these cells to carry anticancer drugs and deliver them with precision to the target cancer cells. This could allow doctors to make surgical strikes against aggressive brain cancers.

Building on previous research

This is not even the first time researchers have hijacked this homing ability of stem cells either. Researchers have previously used the method using neural stem cells to seek and destroy brain cancer in mice and deliver a cancer drug payload[2].

However, this approach has not been widely tested in people due to it being difficult to obtain these neural cells. Currently, to collect such cells you would have to either harvest them from another person or reprogram other adult cells in a two-step process using reprogramming factors to change the cell type.

Unfortunately, harvesting cells requires risky invasive surgery, and reprogramming adult cells and making them into stem cells runs the risk of the cells becoming cancerous. Finally, using cells from other people often triggers an immune rejection response from the immune system.

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Taken together, these issues make the approach impractical and risky, so researchers needed a better way to achieve the same results.

Cellular reprogramming

In answer to the issues mentioned, the research team in this new study decided to see if they could skip a step in the cell reprogramming process. Normally, during the process you have to turn an adult cell into a regular stem cell and then into the desired cell, but the researchers tried something different.

They treated skin cells with a mix of factors that promote neural stem cell properties and it appeared to work. The skin cells turned into the desired cells with only one step, confirming that the process worked as desired.

The researchers then wanted to know if these new cells would home in on tumors. The good news was they did. The researchers observed the cells moving towards the tumors and that they were able to dig into tumors grown in the lab. The cells moved a distance of 500 microns in 22 hours.

Next, the team engineered the cells to deliver payloads of common cancer treatments to tumors in mice. Mouse tumors that were injected directly with the reprogrammed cells shrank between 20 to 50 fold in no more than 28 days.

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Moving to clinical trials

The big question now is how effective this approach will be in a human brain. In the brain, the cells would have to travel much longer distances to reach tumors and may have to move many millimeters or even centimeters, many times farther than the 500 micron distance observed in lab dishes.

The research team is currently working on this question and is now testing how far their homing cells can move using larger animal models. They are also obtaining skin cells from glioblastoma patients to ensure the method works in the people they need to treat.

The research team is hoping to move to human clinical trials as soon as possible and are doing everything they can to speed up the process and ensure their therapy is as safe and efficient as possible.

Conclusion

Cancer is one of the diseases of aging and caused by the hallmark genomic instability. Therefore, progress in bringing cancer under effective control is of great interest to LEAF. This approach so far is very promising.

If we wish to enjoy healthy and longer lives through rejuvenation biotechnology then it is paramount that solutions to cancer are found, and research progress like this makes us extremely hopeful.

The traditional approaches to cancer are moving to more novel and innovative methods using the power of cellular reprogramming and boosting the body’s own defences to fight it.

President Nixon started the war on cancer in 1971; it could be that, in the not-so-distant future, the war will finally be won.

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Literature

[1] Bagó, J. R., Okolie, O., Dumitru, R., Ewend, M. G., Parker, J. S., Vander Werff, R., … & Hingtgen, S. D. (2017). Tumor-homing cytotoxic human induced neural stem cells for cancer therapy. Science translational medicine, 9(375), eaah6510.

[2] Aboody, K. S., Najbauer, J., Metz, M. Z., D’Apuzzo, M., Gutova, M., Annala, A. J., … & Garcia, E. (2013). Neural stem cell–mediated enzyme/prodrug therapy for glioma: Preclinical studies. Science translational medicine, 5(184), 184ra59-184ra59.

[3] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
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About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.