Nanoparticles With Mutant Proteins Used to Fight Cancer Cells

Highlights:

Cancer cells undergo numerous mutations and synthesize mutant proteins
After radiotherapy these mutant proteins are discharged from the cells
The mutant proteins are used with nanoparticles to boost host immune response against cancer

A research team from the University of North Carolina has found a new way to harness the body’s natural ability to destroy cancer cells. After radiation therapy, the cancer cells that are killed release mutant proteins. These proteins are detected by the immune system of the body and function as protein markers that guide the immune system to kill more cancer cells in other parts of the body. The study was published in the journal Nature Nanotechnology recently and it details the potential ability of these proteins to improve the immune defense against cancer cells.

Sticky Nanoparticles

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‘The mutant proteins from cancer cells that are combined with the nanoparticles guide the immune cells against the cancer cells.’

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The research team used ‘sticky’ nanoparticles, also called antigen-capturing nanoparticles, to improve the body’s ability to detect cancer proteins. The proteins that are dispelled by the dying cancer cells could be used to work along with these nanoparticles to boost the immune response against cancer.

Senior author of the study, Dr. Andrew Z. Wang, said that the scientists had hypothesized that if they used nanoparticles to grab the cancer proteins then they would be able to improve the immune defense. Dr. Wang is a member of UNC Lineberger and an associate professor in Radiation Oncology in the UNC School of Medicine. Nanoparticles were found to be attractive to the immune system as their size resembles that of viruses, due to which the immune system responds to nanoparticles.

Radiation Therapy

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This method of treatment is popularly used to treat many different types of cancer. Scientists have always observed an “abscopal effect", wherein, there is shrinkage of the tumor outside of the primary site treated with radiation. This patient study was published in the New England Journal of Medicine (2012) and detailed the abscopal effect in a patient with melanoma.

This effect was due to the immune cells that were called to the tumor site post radiation. The mutated proteins released by the dying cancer cells were used by the immune cells present to train other immune cells to fight against cancer. This effect of the immune cells works alongside the “checkpoint inhibition” of immunotherapy drugs that are used to eliminate the ‘brakes’ of the immune cells in their fight against cancer.

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These mutant proteins, that are discharged from the dying cancer cells, are utilized by the immune system as markers, according to the co-author of the study, Dr. Jonathan Serody, who is an Associate Director for translational research.

Dr. Serody further stated that a lot of mutations are present in cancer cells which get synthesized to mutated proteins; these proteins when exposed to the immune system are treated as foreign. Though the body does not respond to the cancer cells as it recognizes them as its own, the mutant proteins that are discharged from these cancer cells are recognized as foreign.

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Capturing the Mutant Proteins

The research team from UNC Lineberger showed in preclinical studies that the nanoparticles could be used successfully to capture the mutant proteins. Immune cells then take up the nanoparticles while the mutant proteins present on their surface can be used to train the immune cells. This defense system will help in eliminating cancer from the rest of the body.

The study findings were

20% of mice that were treated with the nanoparticles had a complete response when compared to mice that did not receive the treatment.

Dr. Wang said that the nanoparticles were taken up by immune cells and transported to the lymph nodes. These nanoparticles were found to increase the immune response by increasing the number of immune cells that target the cancer cells. There is a need for a strategy that can be used to improve the responses to immunotherapy.

The study shows that there is a potential to improve the immune response of the host, by removing the checkpoint inhibitors, translating into longer survival.

Cancer Immunotherapy

Immunotherapy is a method of treating cancer that is aimed at boosting the immune defenses against cancer. This includes

Stimulating the immune system to improve it
Introducing immune system components that train immune cells to specifically target cancer cells

The nanoparticles that consist of the mutant proteins could be a potent activator of the immune system against the cancer cells. Dr. Wang and his research team are focusing on developing a commercial agent that can be used for treating cancer.

References:

What is cancer immunotherapy? - (https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/what-is-immunotherapy.html)
Immunotherapy - (https://www.cancer.gov/about-cancer/treatment/types/immunotherapy)

Source-Medindia