Researchers discover protein that helps the body target and kill cancer cells

A recent study from researchers based in the UK has identified a protein that is important for targeted-killing of cancer cells, which could lead to new cancer therapies with fewer side effects.

In Short: Scientists figure out how your body can find cancer cells, while leaving the rest of your cells alone

White blood cells form an essential part of the immune system, protecting the body from things like bacteria, viruses, and parasites. Depending on the situation, the body has two lines of defense: innate immunity, which acts like a rapid-response team at the first signs of an infection, and adaptive immunity, which is a slower, more specialized response. Adaptive immunity involves immune cells ‘remembering’ an infection, so they can more quickly respond if the infection happens again, and this is how a vaccination protects against future infections.

T cells are a specialized type of white blood cell that forms an important part of the adaptive immune response. They can recruit other immune cells for a stronger response, prevent targeting of the body’s own cells, and even directly kill cancer cells or virus-infected cell. A special protein on the surface of the cell, called a T cell receptor (TCR), helps it identify each protein that it might want to target and eliminate.

Crowther, Dolton, et al. found that a special type of T cell that can be grown in a lab, called MC.7.G5, was able to target and kill a large range of different cancer cells. MC.7.G5 was able to target and kill prostate, breast, ovarian, colon, lung, bone, melanoma, and leukaemia cancer cells, all while leaving healthy cells alone. A TCR in MC.7.G5 was responsible for this effect.

Next, the scientists wanted to find out what protein the TCR in MC.7.G5 was recognizing. To do this, they performed an experiment (using CRISPR/Cas9) where they effectively ‘delete’ each gene in the genome, one-by-one, in the cancer cells. If a gene is important for identifying a cell as cancerous, deleting that gene in the cancer cell will make that cell unrecognizable to MC.7.G5, letting the cancer cell go unnoticed by the T cells and letting it survive. With this approach, the researchers identified one very-promising gene, called MR1, that makes a protein that lets cancer cells be recognized by T cells.

To learn more about how MR1 might work, the scientists tried to figure out how MC.7.G5 might interact with MR1 to recognize it. Unexpectedly, MR1 doesn’t work like other proteins and might need to bind to another molecule, before the MC.7.G5 T cell can recognize it.

One of the powerful parts of new cancer treatments is that the body’s own cells can be taken out of a patient, given new tools to fight cancer (like TCRs that can recognize different cancers), and be put back into the patient. This can minimize side effects, like those seen with chemotherapy, and may be more effective at eliminating the cancer. 

To apply their research towards this goal, Crowther, Dolton, and their colleagues obtained T cells from patients with advanced melanoma, and put MC.7.G5’s TCR in the patients T cells. This empowered these modified T cells and enabled them to kill melanoma cells, while leaving healthy cells alone. When the researchers made cells cancer cells that did not have MR1 protein anymore, the modified T cells could no longer recognize the melanoma cells. This shows that the TCR and MR1 protein together can work to specifically target cancer cells in patient samples.

Altogether, this research represents a really exciting approach to cancer therapeutics, where the body’s own immune system can be used to effectively kill cancer cells and with fewer side effects. It is quite promising for developing new treatments, and for gaining a better understanding of cancer cells interact with T cells.

The study itself can be accessed here.