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Trial Shows Engineered T-Cells Act on Multiple Myeloma

Multiple myeloma cells

Multiple myeloma characterized by immature plasma cells (National Library of Medicine, NIH)

21 July 2015. An early-stage clinical trial shows immune system cells from patients with the blood-related cancer multiple myeloma — modified to attack a protein suspected of helping the cancer grow — generated a positive clinical response in most of the participants. The team from University of Pennsylvania cancer center, University of Maryland medical school, and biotechnology company AdaptImmune Therapeutics published its findings in yesterday’s issue of the journal Nature Medicine (paid subscription required).

Multiple myeloma is a cancer of plasma cells, white blood cells helping fight infections by making antibodies that recognize invading germs. The disorder causes cancerous cells to accumulate in the bone marrow, crowding out healthy plasma cells. Instead of antibodies, the malfunctioning cancer cells produce abnormal proteins that cause kidney problems. American Cancer Society expects nearly 27,000 new cases of multiple myeloma to occur in the U.S. this year, causing more than 11,000 deaths.

AdaptImmune, in Oxford, U.K. and Philadelphia, Pennsylvania, develops cancer therapies harnessing a patient’s own white blood cells in the immune system known as T-cells. The company’s technology enhances T-cells from their natural state by adding a new gene with more sensitive receptors targeting proteins specifically associated with the patient’s cancer. AdaptImmune was one of the funders of the trial, with National Institutes of Health and Multiple Myeloma Research Foundation.

The targets in this case are NY-ESO-1, an antibody generating protein or antigen found in 60 percent of individuals with multiple myeloma, and associated with cancer cell growth, and an associated antigen LAGE-1. The engineered T-cells are cultured and reproduced in the lab, then infused back to the patient as a therapy, following a transplant of a patient’s own hematopoietic or blood-forming stem cells.

The clinical trial tested engineered T-cell therapy among 20 patients at University of Pennsylvania and University of Maryland medical centers with multiple myeloma, where their disease is not responding to treatment or relapsed. Participants received on average some 2.4 billion engineered T-cells, 2 days after the stem cell transplants.

The study looked primarily at the safety and tolerability of the therapy, particularly for cytokine-release syndrome and macrophage activation syndrome, two adverse reactions associated with immune therapies, that result in fever, nausea, chills, abnormally low blood pressure, and rapid heart rate, among other symptoms. The authors report the treatments were well tolerated, with none of the participants experiencing either of those conditions.

The trial looked as well at activity of the engineered T-cells in the patients. The results show the T-cells travel to the patients’ bone marrow, site of the tumors, and in 18 of the 20 cases stayed there for 2 years following their infusions. And 14 of the 20 participants experienced a complete or near complete response in the 3 months following the treatments.

As of April 2015, with a median follow-up time of 30 months, the median progression-free survival time — amount of time without the disease getting worse — was 19.1 months and median overall survival was 32.1 months. In cases of relapse, say the authors, the patients reported a loss of the modified T-cells, pointing to the need for better measures to improve persistence of the therapy.

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