We are in the thick of one of the most exciting developments in cancer research and treatment today: immunotherapy. This approach involves using highly sophisticated medical interventions to enable the body’s own immune system to fight cancer cells.

Improving CAR-T therapy

One of the great success stories in the field is chimeric antigen receptor-modified T-cell (CAR-T cell) therapy, in which the patient’s blood cells are genetically modified and multiplied in the laboratory, then infused intravenously back into the patient’s body to fight the cancer. The therapy works extraordinarily well in many cases of leukemia, often achieving complete remission, but it frequently triggers a serious immune reaction known as cytokine release syndrome (CRS).

This “cytokine storm” can make patients very ill and can be life-threatening with symptoms ranging from fever and muscle pain to a drop in blood pressure, difficulty breathing and kidney failure, among others. While drug treatment can relieve CRS after it develops, better understanding, earlier intervention and improved management of CRS are critically important for patients undergoing CAR-T cell therapy.

“One team of scientists felt that a combination of immunotherapies...might succeed where the single therapies failed.”

Using biomarkers

In a recent study, researchers identified signals, called biomarkers, that can be measured in patients’ blood and could predict, with remarkable accuracy, which patients will go on to encounter severe CRS after treatment with CAR-T. The findings, which were predominately from pediatric patients, could help predict which patients are likely to develop severe CRS and guide management of treatment for childhood, as well as adult leukemia, including early administration of medication to limit CRS and smooth the patient’s recovery.

The team published its data in Cancer Discovery, a leading journal published by the American Association for Cancer Research, and hopes to test approaches to catch CRS in the early phase in clinical trials. 

Addressing melanoma

Immunotherapy has also been effective in treatment of metastatic melanoma, although many patients do not respond. One team of scientists felt that a combination of immunotherapies, each of which had limited success in this disease when used alone, might succeed where the single therapies failed.

They were right. In a newly released first-in-human study, the team combined an adoptive cell therapy, in which patients are treated with their own natural cancer-fighting immune cells after they are collected and grown in large numbers in the laboratory, with checkpoint blockade therapy, in which drugs are used to ”release the brakes” that cancer cells insidiously place on the patient’s anti-cancer immunity.

Initial success

The researchers treated just 10 patients with the combination treatment; seven of them responded. Two fortunate patients, one of whom had melanoma that had reached stage 3 despite surgery and previous immunotherapies, saw their disease go into complete remission that has lasted for years.

The strategy may hold “broad promise” for development of immunotherapy against melanoma, the researchers wrote in the Journal of Experimental Medicine. They also published results from a related study in the Journal of Clinical Oncology.