Research by scientists at UT Southwestern Medical Center shows that certain immunotherapy agents improved the ability of the immune system to get rid of cancer cells when combined.
The immunity boost led to long-term remission of deadly cancer in mice.
Scientists have made significant strides in recent years in recruiting immune cells to fight certain cancers. Some drugs that promise increased survival for patients came out of their work.
However, researchers have focused more on only a part of immunity and less on another important area.
In the new study, researchers introduced a new perspective to making the immune system fight cancer cells more effectively. Their finding could lead to the development of more useful treatments for people with glioblastoma, a deadly brain cancer.
The study appeared in Nature Communications.
Fighting cancers through improved immunity
There are two types of immunity: innate and adaptive. Innate immunity involves an older system that constantly searches through the body to find and eliminate foreign agents and pathogens, usually by consuming them. Adaptive immunity refers to that a person acquires after being exposed to a pathogen.
These two parts of the immune system are not independent of each other. Adaptive immunity depends on innate immunity to an extent in determining where its help is most needed.
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Scientists have made significant progress in using immunity to combat some cancer types, thereby improving survival rate.
However, researchers achieved their successes mainly by focusing on adaptive immunity. This is according to Wen Jiang, a UT Southwestern Medical Center assistant professor of oncology. Jiang led the current study.
Some therapies in development aim to enhance the action of the innate immune system against cancer cells. These mainly target the CD47 protein that cancer cells use to discourage immune cells from consuming them. However, they show more potential for the treatment of blood cancers and less for fighting solid tumors.
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The most common and most aggressive form of malignant brain tumor in adults is glioblastoma (GBM). Jiang, who sees people with this disorder in his clinic regularly, said patients often show high CD47 levels.
Better treatment approach
Jiang and his fellow researchers were interested in finding a means of boosting innate immunity in GBM patients. They wanted solutions that not only make the innate immune system to eat cancer cells but also direct adaptive immune system to attack tumors.
The research team began by studying the effects of monoclonal antibodies, which typically inhibit CD47, on GBM cells in mice. It grew the cancer cells in Petri dishes with phagocytes, a group of innate immune cells.
Aided by the agent, the phagocytes were able to eat more cancer cells. The researchers, however, found that the outcome was not “too striking.”
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Jiang and his colleagues then decided to use another drug to try and improve the ability of immune cells to consume cancer cells. The medication, known as temozolomide (TMZ), is commonly used for the treatment of GBM patients. It makes tumor cells more open to attack by the immune system through the activation of stress responses.
TMZ boosted the phagocytes’ hunger for tumor cells. However, the researchers still did not find the results very exciting.
The team then decided to use the two drugs together since they attack cancer cells in different ways. It thought that it might be possible to get an improved response when combined.
The combination therapy led to a greater ability of innate immune cells to eat GBM cells as expected. This was in comparison to when the drugs were used separately.
Phagocytes didn’t just stop at eating cancer cells when the drugs were combined. Scientists also found that they go further to use materials from tumors to improve the likelihood of T cells attacking the harmful cells.
T cells are mainly responsible for the ability of adaptive immunity to fight cancer.
More-promising combination therapy
The drugs helped to shrink tumors considerably and prolong life when trialed in a GBM model in mice.
Researchers found, however, that the efficacy of the combination treatment dropped with time. Cancer cells devised a means of keeping immune cells from consuming them.
The tumor cells were able to do this by increasing their PD-L1 production. This protein protects GBM cells from attack by T cells of the immune system.
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The research team, therefore, added an antibody known as anti-PD-1 to the therapy to break down the cells’ resistance. As a result, the survival rate of mice with GBM increased drastically.
The improved combination therapy helped to keep roughly 55 percent of the animals alive while the study lasted. This result is comparable to long-term remission in people with GBM, according to the researchers.
“If a new therapy extends survival by even one or two months, it’s considered a blockbuster drug,” said Jiang. “Here, we’re talking potentially about a significant proportion of patients who could be cured.”
The Harold C. Simmons Comprehensive Cancer Center member stated that being able to connect innate and adaptive immunities could be ground-breaking for the treatment of GBM.
Jiang revealed that the team was hoping to test the combination therapy in human clinical trials soon.
References
https://www.nature.com/articles/s41467-020-15129-8
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