Reprogramming a new type of T cell to go after cancers with less side effects, longer impact

Immunotherapy is one of the more appealing and effective kinds of cancer treatment when it works, but the relatively new approach is still fairly limited in the kinds of cancer it can be used for. Researchers at the Sloan Kettering Institute have discovered a new kind of immune cell and how it could be used to expand the reach of immunotherapy treatments to a much wider pool of patients.

The cells in question are called killer innate-like T cells, a threatening name for a potentially lifesaving innovation. Unlike normal killer T cells, killer innate-like T cells stay active much longer and can burrow further into potentially cancerous tissue to attack tumors. The research team first reported these cells in 2016, but it’s only recently that they were able to properly understand and identify them.

“We think these killer innate-like T cells could be targeted or genetically engineered for cancer therapy,” said the study’s lead author, Ming Li, Ph.D., in a press release. “They may be better at reaching and killing solid tumors than conventional T cells.”

Unlike killer T cells, killer innate-like T cells can identify a wide range of non-mutated antigens, the markers that signal to the body that something is foreign and potentially dangerous, which prompts an immune response. Because the antigens these cells attack are normal, they would cause the immune system to attack healthy tissue, which is why highly responsive T cells are usually killed off.

In this case, however, the research team at Sloan Kettering was able to reprogram the cells to not react to normal antigens and instead respond to IL-15, which many cancer cells produce. Because this molecule is only found in healthy tissues at very low levels, the reprogrammed T cells don’t respond, greatly limiting the possibility of causing harm.

Another promising aspect of the innate T cells is their longevity. Unlike regular killer T cells, these ones don’t produce PD-1, the “programmed cell death” molecule meant to stop cells from living too long. Without this molecule, these new cells can last much longer than the usual T cells. Also unlike T cells, they don’t recirculate through the body and instead burrow into tissue to seek out threats, an attractive feature for finding and combating tumors.

While most of the experiments with these cells have been done with mice, the researchers have confirmed that human tumors have these cells too, and they’re planning to continue studying their use for immunotherapy treatments.