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Activated “killer” T-cells effective against resistant lymphoma

“Killer” T-cells activated in the laboratory to recognize specific antigens on the surface of lymphoma cells proved an effective therapy in a majority of patients with relapsed or recurring cancers of the lymph system or who were at risk for such relapses, said researchers from Baylor College of Medicine in a report that appears in the Journal of Clinical Oncology.

“Most people have these T-cells that are specifically directed against Epstein-Barr virus (a common form of herpesvirus). However, often these cells ‘can’t recognize’ the tumor they should be attacking,” said Dr. Catherine Bollard, corresponding author of the report that was submitted while she was with the Cell and Gene Therapy Center at Baylor College of Medicine, Houston Methodist Hospital and Texas Children’s Hospital. She is now with Children’s National Medical Center in Washington, D.C.

“We take the cells out and re-educate them in culture in the laboratory so that hey regain their ability to attack the tumor,” said Dr. Cliona Rooney, professor in the Center for Cell and Gene Therapy, and one of the paper’s authors.

The laboratory technique does not alter the genetic makeup of the cells unlike other strategies that have been recently used to train T-cells to kill leukemias. Rather, this approach reactivates the ability of the T-cells to recognize tumor cells that express Epstein-Barr virus proteins and destroy them. In this study, patients had either Hodgkin’s or non-Hodgkin’s lymphomas.

The technique involves removing the T-cells out of patient’s blood, activating and growing them in a specialized cell culture facility and returning them to the patient, now ready to attack the tumors.

In the study, the authors prepared and gave the T-cells to each of 29 patients considered at high risk of relapse, as well as to 21 patients who had relapsed or had treatment-resistant disease when they received the infusion. Twenty-eight of the first 29 patients who received the newly activated T-cells as an add-on or adjuvant treatment remained in remission from their disease 3.1 years after treatment. Of the 21 with more severe disease, 13 responded to the treatment and 11 had complete remission without requiring “pre treatment” with chemotherapy.

None of the first group of patients died from their lymphomas but nine died from complications associated with the extensive treatment involving chemotherapy and radiation that they had received as first-line therapy prior to relapse.

“That’s why this research is important,” said Bollard. “Patients with lymphomas traditionally have a good cure rate with chemotherapy and radiation. What kills them is the side effects of those treatments – second cancers, lung and heart disease. This is a targeted therapeutic approach that we hope can be used early in the disease to treat relapse. We saw good outcomes here. Eventually, it could be a front-line therapy.”

While the difficulty of tailoring the T-cells for each patient has been cited as a barrier to this treatment, Rooney pointed out that current treatments are also expensive and induce severe side effects that often require hospitalization.

“Although we spend some time making the cells, patients go home with few side effects and few associated hospital costs,” she said. “It can be less costly than chemotherapy.”

Others who took part in this research include: Stephen Gottschalk, Vicky Torrano, Oumar Diouf, Stephanie Ku, Yasmin Hazrat, George Carrum, Carlos Ramos, Hao Liu, Meng-Fen Wu, Andrea M. Sheehan, Adrian P. Gee, Malcolm K. Brenner and Helen E. Heslop, all of Baylor College of Medicine; Luis Fayad, Elizabeth J. Shpall and Barbara Pro of the University Texas MD Anderson Cancer Center; and Daniel Lee and Youli Zu, of Weill Medical College of Cornell University in New York.

Funding for this work came from the National Institutes of Health (Grants P50CA126752 and PO1 CA94237); the Specialized Center of Research Award from the Leukemia Lymphoma Society; the Dan L. Duncan Chair (held by Heslop); the Fayez Sarofim Chair (held by Brenner); the National Heart, Lung and Blood Institute (Contract HHSN268201000007C); the Clinical Research Center at Texas Children’s Hospital; The Methodist Hospital; The Dan L. Duncan Institute for Clinical and Translational Research at Baylor College of Medicine, shared resources from Dan L. Duncan Cancer Center (National Cancer Institute Grant P30CA125123) and the National Center for Research Resources (Grant U42 RR16578).