Immunotherapy may be the alternative treatment that revolutionizes cancer treatment working with the body instead of against it.

Treatments such as surgery and chemotherapy may not always permanently remove the cancer, depending on its location, type and stage.

Such treatments are designed to eliminate the mutated cancer cells that have already developed and formed tumors, but they dont always stop the body from continuing to produce more cancer cells.

So what if the body could learn to detect and fight mutated cells that fly under the radar?

A study by MU scientist Diana Gil Pags, PhD, about melanoma tumors in mice has shown that altering immune cells can lead to better results with cancer treatment.

Were trying to add to the arsenal of tools from the immune system that you can use against cancer, Gil Pags said. She emphasized the importance of having multiple treatment options for patients with cancer.

Why is it important to have another way? Because not everyone responds to these types of immunotherapies, Gil Pags said.

In fact, our preliminary research shows that if we combine the immunotherapies that are already in the clinic with our approach, there is an added benefit of mice survival and getting control over the tumor.

Immunology is becoming more foundational for cancer research and treatments. MU research technologist Megan Abergel learned about its expanded applications while working alongside Gil Pags.

I really hadnt realized how much immunology is ingrained in cancer research now, Abergel said.

Its really the hot topic and has been for the last couple years at least. I think its really interesting and promising.

Abergel explained the distinctions in cancer as opposed to other illnesses in terms of the bodys response.

When we get cancer, why is our body not able to mount a response? she said. Because its much more complicated, its using our own cells, so our body doesnt necessarily recognize that its foreign.

Gil Pags has been working on an immunotherapy treatment since 2002. She began by studying exactly how specific immune cells, called T-cells, function. She found a structural part of T-cells that allows the cells to identify diseases.

If it (the T-cell) encounters a healthy cell, there wont be a recognition, and the cell will just go around and do nothing, Gil Pags said. But when there is a positive recognition, the T-cell gets reprogrammed and acquires new capabilities that include being cytotoxic, which means killing cells.

By 2007, the study pointed to the possibility that, if their structure could be manipulated, the T-cells threshold for disease detection could be lowered. This means it would be easier for the body to detect mutated cells or any sort of infection.

These mutations also generate signals that make them easily recognized by the immune system, Gil Pags said. But sometimes those signals are subtle, and they are not enough to turn on the mechanism on the T-cells.

In October 2019, Gil Pags received a grant to develop drugs that work with mice genetics to enhance their T-cells. The goal for the drugs is to bind to the proteins that make up the receptors of the T-cell to lower its detection threshold, Gil Pags said.

That data proved that altering the T-cells made it easier for the mice to get rid of the melanoma tumors and keep them away.

The mice have now become what Gil Pags describes as humanized in order to test other drugs that are meant to bind to human T-cells.

A human protein is added to the mice proteins on the T-cell receptors, so the drugs developed for humans can be tested.

With just one component, weve made human in the mouse T-cells, our human reagent binds to these mouse cells now, Gil Pags said.

One problem with the immunotherapy approach is the level of toxicity that a person may experience during treatment.

Gil Pags explained that by lowering the T-cells inhibitions, the cells may also mistake healthy cells for disease, and the therapy can mimic the symptoms of an autoimmune disorder.

Part of the grant is to evaluate the toxicity inherited in our approach and compare it with other immunotherapies already out in the clinic that target T-cells, she said.

If the drug candidates are not equal to or less than the toxicity levels of existing treatments, the research she conducts wont move forward, she said.

The positive outcome is that, so far, we have learned that at least one of our candidates reproduces the anti-tumor effects of our approach seen in mice, and then it might be good enough to move into the clinic in the near future, she said.

She mentioned the possibility that none of the candidates measure up after considering their anti-tumor effects and side effects. Sometimes negative data is not valued so much, but it is needed to push you into developing better ideas.

Her lab research was disrupted in early 2020 because of COVID-19, but she said it began to pick back up in early fall of 2020.

Researchers will continue to run trials with the mice until they are able to do human clinical trials, she said.

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New treatment could fight cancer by teaching the body to detect and fight mutated cells - Columbia Missourian