Velcro-like proteins keep cancer drugs inside the cancer
There are several techniques used to kill cancer, such as chemotherapy and radiotherapy, but the really tricky part is doing so without harming the rest of the body. Cytokines are small proteins that could play a part in immunotherapy, but they've so far not been approved for use, given their toxicity to healthy cells. Now, researchers from MIT have managed to keep cytokines contained in cancer cells, attaching them with proteins that stick like Velcro.
Cytokines are naturally present in the body, as immune cells use them to communicate with each other. While they have shown promise as a strong cancer killer, the problem is they don't discriminate between cancerous and healthy cells. Injecting the molecules directly into the tumor hasn't worked in the past, with the cytokines leaking out into the bloodstream pretty quickly.
So MIT researchers set out to develop a method that would keep the molecules in the tumor where they belong. The idea was to create a Velcro-like lock that anchors cytokines to the cancerous tissue, by adding a protein to the molecules that binds to another protein that's common in tumors but not in healthy cells.
After conducting extensive searches, the team found two proteins that work as the two parts of the locking mechanism. A protein called lumican was chosen to be paired with the cytokines, because it tightly binds to collagen, another protein that's more abundant in tumors than in healthy cells.
While there is collagen in other parts of the body, the team points out that this isn't a problem for this treatment – there's much more of it in the tumor after all, and when injecting the molecules directly into the cancerous area it doesn't escape into the rest of the body.
The researchers tested the treatment on mice, using two cytokines, interleukin-2 and interleukin-12 (IL-2 and IL-12), which have both proven promising but too toxic for human use so far. These molecules were either paired with lumican or used alone, and given to mice with melanoma that had relatively low levels of collagen, to see how well they stuck.
"In addition, all of the cytokine therapies were given alongside a form of systemic therapy, such as a tumor-targeting antibody, a vaccine, a checkpoint blockade, or chimeric antigen receptor (CAR)-T cell therapy, as we wanted to show the potential of combining cytokines with many different immunotherapy modalities," says Noor Momin, lead author of the study.
When cytokines and lumican were used together with other therapies, the survival rates shot up, with some combinations seeing more than 90 percent of the test mice survive. Even when the cytokine/lumican treatments were used without any of the other therapies, the team found that the toxicity problem was eliminated.
The researchers say the next steps are to improve the technique further, as well as investigate how the Velcro locking system could improve other kinds of treatments as well.
The research was published in the journal Science Translational Medicine.