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New study finds better strategy for lymphoma immunotherapy

An extra boost to extend the cancer-fighting power of specially engineered immune system cells proved effective in a preliminary study involving six lymphoma patients, said researchers from the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children's Hospital and The Methodist Hospital in a report in the Journal of Clinical Investigation.

"We're trying to teach our immune system to recognize cancer cells and kill them," said Dr. Carlos Ramos, assistant professor in the Center for Cell and Gene Therapy and a lead author on the paper.

Special immune cells

Researchers at the Center for Cell and Gene Therapy have pioneered the engineering of special immune cells that are given extra abilities to fight cancer. Their strategy combines the ability of an antibody to recognize tumors with the long life and active immunity produced by cellular components called T lymphocytes.

These T lymphocytes can kill diseased cells, including tumor cells. T lymphocytes can be engineered to permanently express on their surface a modified antibody protein that can recognize malignant tumors.

For this study, an antibody that recognizes a protein on the surface of lymphoma cells called CD19 was adapted to form a new a structure called a chimeric antibody receptor (CAR). When the CAR sees the CD19 in the lymphoma, it binds to it and triggers the attached T lymphocyte to kill the tumor cell, leaving healthy cells intact. These modified T lymphocytes recognize and kill tumor cells in the laboratory, but early human studies have been disappointing because the T lymphocytes do not reproduce well and do not last long in the body.

CD28 increases longevity of T lymphocytes

To overcome this, the researchers added a bit of a special stimulatory molecule, called CD28, to increase the numbers and longevity of the T lymphocytes.

"We know this process works very well in the lab," said Ramos. "Prior to this study, we didn't know how safe this would be for patients and whether these differently engineered immune system cells would last longer in the body."

The study included six patients who had lymphomas that had not been treatable before or that had come back. Each patient's own blood cells were modified in the lab and then infused back into the patient's body. Each patient received two kinds of T lymphocytes bearing a CAR, with and without CD28. Measurements showed that the T lymphocytes that contained CD28 expanded better and remained active against the tumor longer than the ones that did not contain it. By measuring the effect of both lymphocytes in each patient, the researchers avoided differences due to variability between patients, Ramos said.

Other BCM researchers involved in this study include Drs. Barbara Savoldo; Enli Liu; Martha P. Mims; George Carrum; Rammurti T. Kamble; Catherine Bollard; Adrian P. Gee; Zhuyong Mei; Hao Liu; Bambi Grilley; Cliona M. Rooney; Helen E. Heslop Malcolm K. Brenner and Gianpietro Dotti. Dr. Michael J. Keating from the University of Texas M. D. Anderson Cancer Center was also involved.

This work was supported in part by the Leukemia and Lymphoma Society Specialized Center of Research and the U.S. Department of Health and Human Services.