Scientists at McMaster University have developed new cancer immunotherapy that is an alternative to chimeric antigen receptor T-cell therapy, or CAR-T. It uses cancer-killing cells- also referred to as ‘natural killer cells genetically engineered outside the body to find and destroy malignant tumors.
The modified killer cells can efficiently distinguish the target cells from healthy cells that bear comparative markers. This destroys targeted cells only- bringing new promise to this part of immunotherapy.
The engineered T-cells used in CAR-T treatment are profoundly successful against some blood-borne cancers yet can’t recognize cancerous and non-cancerous cells. While they offer significant advantages, they are not consistently relevant to all types of cancer. In patients with solid tumors, the T-cells can cause devastating, even lethal side effects.
Scientists wanted treatment with the same power as CAR-T, but which could be used safely against solid-tumor cancers.
Scientists first propagated natural killer cells taken from the blood of patients with breast cancer. They then genetically modified them to target specific receptors on cancer cells, successfully testing the CAR-NK cells in the laboratory on tumor cells derived from breast cancer patients.
Lead author Ana Portillo, a Ph.D. candidate in the Department of Medicine, said, “We want to be able to attack these malignancies that have been so resistant to other treatments. The efficacy we see with CAR-NK cells in the laboratory is very promising, and seeing that this immunotherapy cancer treatment is feasible is very important. Now, we have much better and safer options for solid tumors.”
McMaster University scientist Ali Ashkar said, “These CAR-NK cells are a little bit smarter, in a way, in that they only kill the enemy cells and not good cells that happen to have the same marker. These cells have a sober second thought that says, ‘I recognize this target, but is this targeted part of a healthy cell or a cancer cell?’ They can leave the healthy cells alone and kill the cancer cells.”
“These are very exciting results, as to date, the benefits of immunotherapy in breast cancer have lagged behind that of other malignancies. These engineered CAR-NK cells are an important step towards having a viable immunotherapy option in this large group of patients.”
“There is good reason to believe the technology would have a similar effect on solid tumors associated with lung, ovarian and other cancers.”
- Ana L. Portillo et al. Expanded human NK cells armed with CAR uncouple potent anti-tumor activity from off-tumor toxicity against solid tumors. DOI: 10.1016/j.isci.2021.102619