Immunotherapy breakthrough recruits more immune cells to fight cancer

The immune system is one of the most powerful tools we have in the fight against cancer, but sometimes it needs a little extra help. In a new study from the Peter MacCallum Cancer Centre, researchers have developed a new way to summon a wider variety of immune cells to target tumors.

One of the most promising forms of immunotherapy is chimeric antigen receptor (CAR) T-cell therapy. This involves removing immune cells from a patient, engineering them to attack a certain type of cancer cell, then injecting them back into the body to hunt down the disease.

This technique has shown particular promise against cancers of the blood, like leukemia, but hasn’t performed as well against solid tumors. According to the researchers on the new study, that’s largely because solid tumors have too wide a range of cell types and proteins.

“One of the major impediments to effective T cell therapy is that in many cases not all cancer cells within a single tumor look the same,” says Paul Beavis, senior author of the study. “In fact, it is common to have high variability of the target protein recognized by the CAR T-cells inside the same tumor, an effect known as heterogeneity. Engineered CAR T cells are very effective at killing the cancer cells that express the target protein. But, unfortunately they are not very good at finding cancer cells that lack this target protein.”

So for the new project, the Peter Mac team set out to find a way to make them more effective. The idea was to recruit other types of immune cells to the tumor site to aid the engineered T cells. Of particular interest were dendritic cells (DCs), which effectively teach T cells what to hunt down.

The researchers engineered T cells that secrete a certain growth factor that attracts more DCs to the tumor. There, they’re able to set off a stronger immune response against the cancer. Mouse tests proved promising.

“When we placed these engineered T cells into mice with tumors we found they were able to trigger an influx of DCs into tumors,” says Junyun Lai, co-lead author of the study. “When we combined the engineered T cells with drugs that further activate immune cells, we found that we could shrink tumors far more effectively. What was really exciting about this approach is that we were able to stimulate the body’s immune system to attack multiple targets on cancer cells, helping to overcome the issue of heterogeneity.”

The team says that dendritic cells might be the key to improved immunotherapies. Other studies have investigated ways to inject stimulants into the tumor itself to rally dendritic cells, or give them snippets of cancer RNA to learn what to attack.

The research was published in the journal Nature Immunology.

Source: Peter MacCallum Cancer Centre

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