JCAR017 is an investigational immunotherapy being developed by Juno Therapeutics to treat patients with aggressive forms of B-cell non-Hodgkin’s lymphoma (NHL) who have not responded well to other treatments. A type of chimeric antigen receptor (CAR) T-cell therapy, JCAR017 uses the patient’s own immune cells to destroy cancer cells.

 How JCAR017 works

To make JCAR017 a patient’s own T-cells are harvested from a blood sample, then modified in the laboratory to recognize CD19, a protein found on the surface of cancerous B-cells. Scientists insert a gene into the cells to cause them to produce a CAR protein that detects CD19. When the modified T-cells are infused back into the patient’s bloodstream, they seek out and destroy CD19-positive cancer cells, causing the tumors to shrink.

JCAR017 differs from other types of CAR T-cell therapies that target CD19 because it balances the number of T-helper cells (the cells that coordinate seek-and-destroy missions), and killer T-cells (the cells that directly destroy the cancer cells). This is thought to optimize the drug’s anti-tumor activity while limiting its toxic side effects.

JCAR017 in clinical trials

An open-label, multicenter Phase 1 clinical trial called TRANSCEND (NCT02631044) is now examining whether JCAR017 is safe and effective in about 270 patients with forms of aggressive, relapsing or refractory B-cell NHL.  Refractory means that the cancer has not responded to any prior treatments, and relapsing means the cancer returned after a successful treatment.

The trial consists of two groups of patients; one group will receive one dose of JCAR017 by intravenous injection and the other will receive two doses by IV. Over the course of the trial, the dose and schedule will be evaluated and modified depending on how effectiveness and safety data.

Juno announced updated results based on data from 71 patients in June who had been treated since the trial began in December 2015.  At three months’ post-treatment, 51 percent of patients had responded, with 39 percent showing a complete response. In the “core group,” a subset of patients who will proceed to the next trial, 66 percent responded at three months, and 90 percent of those patients were still responding at six months.

In September 2017, doctors reported a case of a 68-year-old woman whose brain tumor disappeared after JCAR017 treatment and has remained in remission for a full year.

The trial is still recruiting B-cell NHL patients at sites across the U.S.; enrollment and other information is available here.

Additional information

In December 2017, based on early results from the TRANSCEND trial, the U.S. Food and Drug Administration (FDA) designated JCAR017 a breakthrough therapy for aggressive relapsing or refractory B-cell NHL, and the European Medicines Agency (EMA) granted JCAR017 access to it priority medicines scheme. Such designations help speed the time it takes for a potential treatment to move through the development and approval process.

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