Wed. Apr 17th, 2024

Researchers used an antibody to target mutated proteins in cancer with fewer side effects than common treatments in a promising study on mice.

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Millions of cancer cases are diagnosed globally each year and yet common treatments like chemotherapy and radiotherapy used to target cancerous cells have severe side effects.

Now, researchers from Duke University have described an approach that they say is less toxic than current therapies.

They published their findings in the journal Immunity.

“This is a proof-of-concept study, but the results are very promising,” said Jose Conejo-Garcia, a professor of immunology at Duke University.

Using an antibody to target a mutation

The study focused on a particular type of antibody called dimeric IgA (digA), one of the forms of Immunoglobulin A, the most common antibody that can be found in mucous membranes, like the intestine.

This antibody could be used to target mutations linked with a protein in cancer cells.

In this case, researchers targeted a KRAS G12D mutation.

Normally, the KRAS gene helps control cell growth, but when it’s mutated, it gets stuck in the “on” position, causing cells to grow and divide uncontrollably.

This leads to the development of cancer because the cells keep multiplying when they shouldn’t. KRAS mutations are present in many types of cancers, and they make the cancer more aggressive and harder to treat.

How does it work?

The dIgA binds to mutated proteins to take them out of the cell in a process called transcytosis. That is when a cell takes in something from outside, carries it through the cell, and then releases it on the other side.

“This is a new way of targeting tumour cells by using an antibody that is exquisitely specific for point mutations or molecules that are truly tumour specific,” said Conejo-Garcia in a statement.

“By neutralising them and ensuring these tumour-promoting molecules are expelled outside the cell, we can halt tumour growth.”

When tested in mice with lung and colon cancer, the KRAS G12D-specific antibody was more effective at reducing tumours than current treatments.

Researchers found similar results with another cancer mutation, IDH1 R132H.

“The immune system is the only system in the body that has two key properties that make it ideal for cancer treatment: specificity and memory,” said Conejo-Garcia

The immune system can specifically target tumour cells and it can also remember those cells to mount a more effective attack if the cancer returns, a statement from Duke University said.

Researchers are refining the antibody to make it easier to produce and administer to patients, to eventually test it in clinical trials, the statement added.

According to researchers, these antibodies have the potential for use as targeted therapy against mutations for a multitude of cancers such as ovarian, skin, colon, cervical, prostate, breast, and lung cancer.

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